Sweet Potato Skins Recipe Makes Best Football Party Appetizer

By electricdiet / October 6, 2020


Quick Sweet Potato Skins Recipe Most Delicious Sweet Potato Appetizer for Football Party

Who doesn’t like potato skins? Wait until you try this Sweet Potato Skins recipe!  These healthy sweet potato skins make the most amazing, make-ahead healthy sweet potato appetizer.   Watching football, tailgating or watching the Super bowl, this #1 bar food is everyone’s favorite. Who doesn’t like potato skins? Men and women, and kids of all ages will enjoy these Sweet Potato Skin appetizers from Holly Clegg’s KITCHEN 101 cookbook. A mix of sweet and savory with the naturally sweet potatoes, topped with turkey bacon, cheese and a sprinkle of green onions. You might be surprised to find out this tops everyone’s favorite diabetic sweet potato recipes. Easy, make ahead and fantastic!

Sweet Potato Skins
Yes, this is an easy healthy recipe and only has four ingredients.  I like make-ahead recipes so you can prepare on your own time frame. My healthy sweet potato skins recipe makes the best sweet potato appetizer ever. Potato skin appetizers gets a deliciously healthy spin with fiber-rich sweet potatoes and healthier ingredients ideal for any appetizer or snack.

    Servings12 potato skins

    Ingredients

    • 6


      medium sweet potatoes

    • 4slices


      turkey baconcooked and crumbled

    • 1/2cup


      green onionschopped

    • 2/3cup


      reduced-fat shredded Cheddar cheese

    Instructions
    1. Wash potatoes well, and dry thoroughly. Microwave on high 8-10 minutes depending on size (or in 425˚F oven bake 50-60 minutes). When potatoes cool to handle, cut in half lengthwise; scoop out pulp, leaving a 1/4-inch shell (save pulp for another use). Cut potato skins in half width-wise.


    2. Place potato skins on baking sheet lined with foil. Coat skins with nonstick cooking spray.


    3. Bake 475°F for 5-7 minutes; turn and coat skins on other side with nonstick cooking spray. Bake until crisp, 3-5 minutes more.


    4. In small bowl, mix together bacon, green onions, and cheese.


    5. Sprinkle mixture inside skins. Bake 2 minutes longer or until cheese is melted.

    Recipe Notes

    Per Serving: Calories 79, Calories from Fat 25%, Fat 2g, Saturated Fat 1g, Cholesterol 7mg, Sodium 155mg, Carbohydrates 11g, Dietary Fiber 2g, Total Sugars 2g, Protein 4g, Dietary Exchanges: 1 starch, 1/2 lean meat

    Building On Basics Chapter In KITCHEN 101 Cookbook

    Who doesn’t like burgers, tacos, potatoes and pizza?  This delicious and diabetic Sweet Potato Skins recipe is from the Building On Basics Chapter in Holly Clegg’s easiest cookbook, KITCHEN 101.  There is even a chapter that gives you healthier options for some of your favorite junk food!

    We think of potato skins when watching football but remember these wonderful pick ups year round.  .

    sweet potato skins recipe best sweet potato appetizers

    Healthy Sweet Potato Skins Nutritious, Fabulous and Flavorful Sweet Potato Appetizer

    healthy sweet potato skins that are diabetic sweet potato recipes

    What makes these sweet potato skins healthy? Sweet potatoes are a complex carbohydrate, good source of fiber; and they also fight inflammation as their orange color is from the Carotenoid antioxidant which turns into Vitamin A. Besides, they are moist, naturally sweet and delicious!

    Sweet potatoes are also low in fat and sodium, and a good source of Vitamins C and E! This is a diabetic sweet potato skins recipe and check out these other delicious healthy sweet potato recipes! Holly’s arthritis cookbook includes so many good sweet potato recipes also because they are such a good source of antioxidants.

    What To Do with The Extra Sweet Potato Pulp from The Sweet Potato Skins Recipe

    When preparing this healthy sweet potato skins recipe – don’t let the extra pulp go to waste! Make mashed sweet potatoes by mixing in skim milk, sour cream, salt and pepper and maybe a dash of cinnamon for a yummy side dish another day. You could also use the extra mashed sweet potatoes in Holly’s Yummy Yam Coffee Cake or the best Crawfish and Sweet Potato Bisque recipe. 

    Do You Have A Potato Masher?

    Do you have a potato masher? Everyone needs this simple kitchen gadget to mash potatoes or sweet potatoes. After you make the sweet potato skins you can mash the pulp for so many different recipes.

    A potato masher is important because if you beat the potatoes in a mixer they can become starchy so this is really a useful kitchen tool!

    Get Top 25 FAST & FABULOUS FOOTBALL TAILGATING RECIPES

    tailgating recipes

    You will love Holly’s 25 Favorite Football Tailgating Recipes available for only $1.99! Included are dips, pick-ups, hearty food and the best of Holly’s sweet treats.  Best of all, it comes with a SHOPPING LIST so all the work is done for you from your menu to your grocery run.

    Healthier and EASY-TO-MAKE recipes with the nutritional information.  If you have health concerns, gluten-free and diabetic-recipes are highlighted.  DOWNLOAD  this great menu of party option.

    Get All of Holly’s Healthy Easy Cookbooks

    The post Sweet Potato Skins Recipe Makes Best Football Party Appetizer appeared first on The Healthy Cooking Blog.



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    Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

    By electricdiet / October 4, 2020


    By definition, LADA patients have functioning β-cells at diagnosis indicating that it is imperative to implement therapeutic strategies targeted to improve metabolic control but also to preserve the insulin-secreting capacity (53). To make a proposal for treatment of LADA, the panel reviewed current clinical trial data and reiterated the conclusions of the Cochrane Review regarding lack of good-quality, large-scale, controlled trials with long-term follow-up (54). As mentioned earlier, the criteria used to define LADA are shown in Table 1. Of note, our proposal only applies to patients who initially were considered not to need insulin.

    Hypoglycemic Agents

    Insulin Sensitizers (Metformin, Thiazolidinediones).

    The majority of LADA patients are clinically diagnosed as having T2D and treated initially with metformin before they are identified as having LADA. The panel concluded that although there is little evidence for the use of metformin, there is no evidence against its use. Metformin can increase insulin sensitivity in T1D (55) without evidence that it could improve long-term glycemic control; in addition, it might reduce weight, LDL cholesterol levels, and the risk of atherosclerosis progression (56). Results from ongoing clinical trials, investigating the effects in LADA patients of monotherapy/adjunct metformin on metabolic control, β-cell function, and tolerability, will provide more evidence on the precise role of metformin.

    In a small study (n = 23 patients), thiazolidinediones (TZD), when combined with insulin, preserved β-cell function in LADA, although the study needs to be replicated (57).

    In a four-arm, randomized trial performed in 54 Chinese subjects, LADA patients were assigned to either sulfonylurea (SU) (n = 14) or rosiglitazone (n = 15) therapy if GADA was <175 units/mL and fasting C-peptide was >0.3 nmol/L. While fasting C-peptide was not different between the two groups, C-peptide levels post–oral glucose and delta C-peptide were higher with rosiglitazone as compared with the SU group after 18 months and up to 36 months (P < 0.05 for all comparisons) (58).

    The panel concluded that there is limited evidence supporting the use of metformin and few studies using TZD, so the efficacy of both compounds appears inconclusive. For TZD, the potential risk of atypical bone fractures, macular edema, and weight gain could be a limitation to the use of these compounds.

    Insulin.

    While therapy with insulin is essential in all cases with undetectable C-peptide, patients diagnosed with LADA have, by definition, residual β-cell function and, in general, slow progression toward insulin dependency. A major question is whether insulin therapy should be the initial treatment for LADA (59). There are no data from large randomized, controlled trials with sufficient length of follow-up to draw a conclusion. A Japanese randomized trial comparing insulin (n = 30) with an SU (n = 30) over a 5-year period showed significantly better integrated C‐peptide response with insulin. Thus, in the insulin-treated group, progression to insulin-requiring diabetes was lower compared with SU (P = 0.003) (60). On the other hand, Thunander et al. (61) concluded that early insulin treatment for LADA did not lead to preservation of β-cell function (n = 37), although it was well tolerated and resulted in better metabolic control (in the control group but not in the insulin-treated group, HbA1c increased significantly at 36 months compared with baseline [P = 0.006], while C-peptide decline was progressive, irrespective of age, sex, BMI, HbA1c values, and autoantibody levels). Interestingly, UKPDS found that 11.6% of patients were autoantibody-positive and that they tended to require insulin treatment sooner, irrespective of other allocated therapy (4,62). The data available, although limited, indicate that insulin intervention is effective for metabolic control in LADA patients. However, it remains to be established whether insulin should be administered at an early stage of the clinical disease or whether it is the optimal therapy regardless of the stage of the disease process. Further studies are needed to clarify the impact of insulin therapy and the optimum time for intervention.

    The panel concluded that insulin intervention is effective and safe for LADA patients; however, it still remains to be established whether insulin should be administered in the early stages of LADA, especially when substantial residual β-cell function is present.

    Sulfonylureas.

    As with previous agents discussed, there is limited evidence to suggest the efficacy of SU in subjects with LADA (19). In a multicenter, randomized, nonblinded clinical study, Japanese patients with LADA, randomized to insulin or glibenclamide (n = 30 in each group), were followed for up to 5 years. During follow-up, the SU group had worse metabolic control and a more rapid decline in C-peptide level compared with the group treated with insulin (P = 0.005) (63). More recently, a post hoc exploratory analysis of a small subgroup of LADA patients (n = 38), enrolled in a randomized, controlled trial comparing glimepiride and linagliptin (n = 21 linagliptin, n = 17 glimepiride) at 28 weeks as add-on therapy to metformin in T2D, revealed that despite similar glycemic efficacy, fasting C-peptide at 28, 52, and 104 weeks decreased in patients treated with glimepiride. Conversely, an increase in C-peptide level was observed in those subjects treated with linagliptin; the difference between groups was significant at 28 and 58 weeks (P < 0.01 for all comparisons) (64). As previously described, in a four-arm pilot, randomized, controlled trial performed in 54 Chinese subjects with LADA, comparison of 3-year follow-up data between subjects treated with SU (n = 14) showed a lower delta C-peptide as well as C-peptide after 2-h 75-g glucose load compared with patients treated with rosiglitazone (n = 15) (P < 0.05 for all comparisons), with no differences in glycemic control (58). Overall, the current data are inconclusive, but it cannot be excluded that treatment of LADA with SU results in a decreased insulin secretion. SU are not therefore recommended for the treatment of LADA, nor are they generally recommended as first-line therapy for T2D.

    The panel concluded that sulfonylureas are not recommended for the treatment of LADA, as deterioration of β-cell function as a consequence of this treatment cannot be ruled out.

    Dipeptidyl Peptidase 4 Inhibitors.

    Small clinical trials with dipeptidyl peptidase 4 inhibitors (DPP‐4i) in patients with LADA suggest that this class of hypoglycemic agents might improve glycemic control and preserve β‐cell function with a good safety profile compared with placebo, glimepiride, and pioglitazone (6466). In a post hoc analysis of pooled data from five randomized, placebo-controlled studies (n = 2,709), saxagliptin improved β-cell function as assessed by HOMA2 of β-cell function and postprandial C-peptide from baseline in both GADA-positive (n = 98) and GADA-negative subjects (n = 1,849) (67). A recent study (68) compared the outcome of glucagon-stimulated C-peptide tests after 21-month treatment with either insulin or sitagliptin in GADA-positive LADA patients (n = 64) without any clinical indication for insulin treatment less than 3 years from diagnosis. The metabolic control during intervention did not differ between the two treatment arms, and post-intervention β-cell function was similar in the insulin- and sitagliptin-treated patients. Of note, the stimulated C-peptide response deteriorated significantly more in the group with high GADA level compared with the group with low level regardless of the treatment. Another small study (n = 30) found that sitagliptin, as an add-on treatment to insulin, had a beneficial effect on C-peptide decline compared with insulin alone (65).

    Moreover, a recent trial evaluated the effect of saxagliptin in combination with vitamin D3 in subjects with LADA with promising results (69). Although these studies have several limitations (i.e., post hoc analyses, small sample size, short periods of follow-up, interstudy heterogeneity), DPP-4i agents represent a potential therapeutic alternative for effective management of LADA.

    The panel concluded that DPP-4i may improve glycemic control in LADA patients with a good safety profile. Larger randomized studies are warranted to prove that DPP-4i might preserve C-peptide secretion.

    Sodium–Glucose Cotransporter 2 Inhibitors.

    Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve glycemic control without hypoglycemia and are currently used for the management of T2D. Although no interventional studies have been conducted in LADA patients, international, multicenter, randomized clinical trials in over 5,000 T1D patients confirm the efficacy and safety of adding SGLT2i to existing insulin regimens (7077). One SGLT2i, dapagliflozin, has been recently approved by the European Medicines Agency for use in adults with T1D with BMI of at least 27 kg/m2 who failed to achieve adequate glycemic control despite optimal insulin therapy. However, in the U.S., the use of SGLT2i in T1D still remains off-label. The approval was based on data from phase III DEPICT clinical program (70). SGLT inhibition confers additional benefits in terms of HbA1c reduction, reduced glucose variability, small reduction in weight, and reduced total daily insulin doses without increasing the risk of hypoglycemia. However, there is an increased risk of ketoacidosis, often not associated with hyperglycemia, especially in patients not overweight (BMI <27 kg/m2). This feature is of special importance in those LADA patients with medium to low C-peptide levels and not on insulin, considering their increased risk of developing insulin deficiency. Treatment with SGLT2i might mask the signs of progression to insulin deficiency (often presenting as postprandial hyperglycemia) and yet increase the risk of ketoacidosis; therefore, patients should be advised to monitor for ketosis, i.e., measure ketonemia and ketonuria regularly, even daily, as recommended (78), and to discontinue SGLT2i prior to scheduling surgical procedures or exposure to metabolically stressful conditions associated with potential symptoms or signs of ketoacidosis.

    The panel concluded that the approved use of SGLT2i in both T2D and selected T1D patients, in particular those overweight, suggests that they may be promising agents in LADA. However, no studies have been performed in LADA and attention should be paid to ketoacidosis in patients with medium to low C-peptide.

    Glucagon‐Like Peptide 1 Receptor Agonists.

    Glucagon‐like peptide 1 receptor agonists (GLP‐1RA) reduce hyperglycemia (with low rates of hypoglycemia), reduce and maintain weight control, and may suppress appetite, reduce food intake, and slow gastric emptying. A post hoc analysis of pooled data from three randomized phase III trials (AWARD-2, -4, and -5; patients with GADA assessment) indicated that dulaglutide is effective in reducing HbA1c in LADA patients. Dulaglutide treatment resulted in a comparable decrease in HbA1c values in GADA-negative (−1.09%) and GADA-positive (−0.94%) patients at 1 year post-diagnosis, and it appears to be slightly more effective in LADA patients with low autoantibody levels compared with those with high autoantibody levels (79). However, as expected, there was a reduced glycemic response to GLP-1RA analogs (exenatide/liraglutide) in a small patient group (n = 19) with diabetes-associated autoantibodies and low fasting C-peptide levels (≤0.25 nmol/L) (80). Large-scale, prospective, randomized trials with long-term follow-up are required to confirm the efficacy of GLP‐1RA in preserving metabolic control and delaying progression to insulin dependence in LADA.

    The panel concluded that GLP-1RA have shown beneficial results in terms of improving metabolic control in LADA patients unless C-peptide levels are very low. These drugs are approved in T2D and in insulin-treated patients, but more evidence is required in patients with LADA.

    Immune Intervention

    There is only one immune intervention study in LADA patients. Alum-formulated recombinant GADA (GAD-alum) was used in a small phase 2 study that was placebo-controlled with dose escalation in GADA-positive non–insulin-requiring patients (n = 47), who received subcutaneous injections of GAD-alum in different doses (81). The primary outcome was safety as assessed by neurological tests, medication use, and β-cell function evaluated over 5 years, representing the end of the trial (82). No severe study-related adverse events occurred during the 5-year follow-up, and active treatment was not associated with increased risk of starting insulin treatment compared with placebo. After 5 years, fasting C-peptide levels declined in the placebo group compared with the two highest dose intervention groups. The authors concluded that in this small study, the primary outcome of safety was achieved, with evidence of a beneficial effect on β-cell function. A more extensive trial is required before such treatment can be recommended and is currently under way.

    The panel concluded that current data on immune intervention in LADA are very limited, and more extensive phase 2 studies are required before drawing any conclusions.

    Lifestyle Modifications

    LADA is associated with factors that favor insulin resistance and T2D, including low birth weight, overweight/obesity, physical inactivity, smoking, and consumption of sweetened drinks (12). The role of obesity and insulin resistance as risk factors for LADA is abundantly documented (83). It may therefore be possible to treat LADA by a combination of lifestyle changes much as is done in T2D. Among these, medically assisted weight loss if necessary, increased physical activity, and cessation of smoking should be promoted. Thus, intervention studies examining the role of lifestyle factors in the development of LADA are necessary, as our current knowledge is hampered because the small number of studies were conducted exclusively in Scandinavian populations (83).

    The panel concluded that lifestyle modifications are important in treatment of T2D. Intervention studies examining the role of weight reduction and physical activity in the development of LADA are required.



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    10 Diabetic Smoothie Recipes (Low Carb)

    By electricdiet / October 2, 2020


    Looking for a delicious, healthy smoothie to power up your morning? Try one of these low-carb and super tasty diabetic smoothie recipes!

    Collage of low-carb smoothies

    Are smoothies good for you?

    The answer is a little complicated… basically, yes and no. Before we dive into my favorite diabetic smoothie recipes, let’s talk about why.

    Smoothies have become popular as a healthy, easy breakfast or snack you can enjoy on-the-go. However, not all smoothies are created equal.

    In fact, many of the smoothies you can buy at a shop or the store are actually packed with sugar and unhealthy ingredients. Some are as bad as eating a candy bar!

    The trick to making healthy smoothies? It’s all in the ingredients.

    What is a diabetic smoothie?

    This list of diabetic-friendly smoothies includes delicious, easy recipes that are low in carbs and don’t have any added sugar. Bonus points if they pack in some protein and are a good source of fiber.

    Because when you enjoy a healthy smoothie made from nutritious ingredients, it will fill you up and give you energy for hours! No blood sugar spikes, no feeling hungry an hour later.

    Plus, they’re pretty tasty. So whether you want a great on-the-go breakfast or an afternoon pick-me-up, this list has something for everyone!

    With so many delicious options, you might find yourself making smoothies all the time.

    And when the recipes are this healthy and nutritious, why not? It’s a great way to boost your day!

    Other healthy on-the-go breakfast recipes

    Need a healthy breakfast that’s easy to throw together and can be be taken with you? Look no further! Here are a few of my favorite easy recipes to energize my morning:

    If you try any of these recipes, don’t forget to leave a comment below and let me know how you liked them!



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    Pumpkin Chicken Chili – My Bizzy Kitchen

    By electricdiet / September 30, 2020


    I know pumpkin chicken chili sounds weird, but this is an amazing chili. My friend Ally (here is here blog!) recently came out with an eCookbook and I immediately bought it.  She had a recipe for a beef pumpkin chili and since I was using stuff I had on hand, subbed in ground chicken for the beef.  I grind my own chicken though!

    this is a picture of pumpkin chicken chili

    How to Grind Your Own Chicken

    Whenever recipes called for ground chicken I would always search for ground chicken breast, which not only was hard to find where I live, but when I looked at ground chicken with dark meat I just imagined that they took all the chicken scraps, ground it up and then slapped a ground chicken label on it.  Gross.

    All you need to do is dice up chicken breasts and pulse the chicken until it gets to ground chicken texture.  Do not turn your food processor on and walk away, otherwise you will end up with ground chicken paste.  Maybe good for some recipes, but not for this chili.

    Can you taste the pumpkin in the Pumpkin Chicken Chili?

    Actually, I can barely taste the pumpkin and it has a whole 15 ounce can in there (not the 1 cup Ally’s recipe called for).  I think it adds a depth of flavor but something you won’t be able to put your finger on.  

    Pumpkin Chicken Chili

    This is a savory chili that is perfect on a cool fall day.

    Prep Time5 mins

    Cook Time30 mins

    Course: dinner, Main Course

    Servings: 8

    Calories: 278kcal

    • 2 pounds chicken breast ground
    • 4 cloves garlic minced
    • 5 tbsp chili powder
    • 1 tsp cumin
    • 1 tsp cayenne pepper
    • 15 oz canned pumpkin
    • 15 oz tomato sauce
    • 15 oz fire roasted tomatoes
    • 1 cup cooked black beans
    • 1 cup kidney beans
    • 1 cup chili beans do not drain
    • 1 tsp salt optional

    Calories: 278kcal | Carbohydrates: 28g | Protein: 32g | Fat: 5g | Saturated Fat: 1g | Cholesterol: 73mg | Sodium: 1098mg | Potassium: 1126mg | Fiber: 9g | Sugar: 7g | Vitamin A: 10336IU | Vitamin C: 10mg | Calcium: 86mg | Iron: 5mg

    I am already ready for fall weather, fall food and I am 100% #teampumpkin – bring it on!  If you love pumpkin, check out my pumpkin mac n cheese!

    this is a picture of pumpkin macaroni and cheese

    So two questions:  are you team pumpkin?  Are you ready for cooler weather or wish it were still summer?  My friend Morgan is still pulling tomatoes from her garden so I know some of you are still grasping at summer.  I am happy at 57 degrees. 😁

    Be sure to let me know if you make this!  

    Until next time, be well. 





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    How To Measure Your A1C at Home

    By electricdiet / September 28, 2020


    The A1C or Hemoglobin A1C test is something everyone living with diabetes should be familiar with.

    It doesn’t show the whole picture of your diabetes management, but it can be a great indicator of whether your average blood sugar levels are within a healthy range.

    Today, I’ll show you how to easily and accurately measure your A1C at home.

    We’ll also discuss what an A1C test actually tells you, why it’s a relevant test, and how to interpret the results.

    Home A1C test kit and the box it came in

    What is an A1C test

    The A1C test is a blood test that reflects your average blood glucose over the last 3 months. It is reported as a percentage and people who don’t live with diabetes generally have an A1C below 5.7%.

    That means that an A1C test can be a good starting point for a diabetes diagnosis as well as an indicator of whether your diabetes management approach is successful.

    The American Diabetes Association has established the following A1C guidelines for using the test as part of a diabetes diagnosis:

    Table of A1c levels and what they mean

    A1C targets for people living with diabetes should be tailored to the individual, but generally, an A1C of 7% or lower is recommended. An A1C of 7% translates to an average blood sugar of around 154 mg/dl (8.6 mmol/L).

    Some people living with diabetes strive for A1C levels below 5.7%, but aiming for a very low A1C is not always advisable, especially if it’s achieved through an excessive amount of hypoglycemia (low blood sugar).

    Discuss your target A1C with your doctor and remember that it can always be adjusted up or down depending on what’s appropriate for you.

    Why is it important to measure your A1C

    Since elevated blood sugars can lead to a number of short- and long-term complications, it’s advisable to keep an eye on your A1C and ensure that it’s held at a healthy level.

    If you find that your blood sugars (and thereby your A1C) are increasing above your target, there are several things you can do to reduce them, such as discussing adjusting your medication with your doctor, changing your diet, and making lifestyle changes

    You can read our complete guide to lowering your A1C for more information.

    Since the A1C tests give you a picture of your blood sugar level for the last 3 months, it makes sense to have your A1C measured at least every 3 months to keep track of how your blood sugars are progressing.

    It the test is used for a diabetes diagnosis, you might have to also have your fasting blood sugar and antibody levels measured to determine which type of diabetes you live with, such as type 1 or type 2 diabetes.

    How to use the A1C home test kit

    There can be many reasons to measure your A1C at home, such as limited access to see your doctor, the distance to a lab, the cost of the lab work, etc.

    There are great options for measuring your A1C at home, but please consult with your medical team before making any changes to your care or self-diagnosing diabetes.

    One very affordable A1C home test kit is the A1CNow SelfCheck which I demonstrate how to use in the video below.

    The kit comes with 4 A1C tests and will give you your A1C result in only 5 minutes. Follow the instructions that come with the kit and make sure to add enough blood or it will return an error message.

    Are home A1C test kits accurate?

    Most home A1C kits are considered to be as accurate as lab A1C tests. The results are accurate within plus/minus 0.5 percentage points, which is about the same as most lab results.

    To ensure accuracy, look for products that are NGSP-certified (National Glycohemoglobin Standardization Program) and/or have FDA-clearance or CE-mark. All the products mentioned in this article are NGSP-certified.

    When I tried the A1CNow SelfCheck at home (see the video above), the A1C results came back with exactly the same result as the A1C lab test I had done a few days earlier (I used Quest Diagnostics for the lab test).

    How much does an A1C test kit cost?

    The A1CNow SelfCheck I used in the video is $53.83 on Amazon (as of September 2020) for 4 tests. I chose this kit as it was the cheapest solution, but similar home A1C kits can be found on Amazon ranging from $60-$100 for 4 tests.

    You can also find home A1C kits in most pharmacies such as CVS and at Walmart.

    A1C kits that require you to collect a blood sample at home and send it to a lab is also available. One FDA-cleared kit that I’ve tried is the Home Access Health home A1C test which was $40 (as of September 2020).

    These tests require a significantly larger blood collection (4-5 large droplets) and you can end up waiting up to 4 weeks (like I did when I tried it out) for your test results, depending on how fast the mail gets to the lab and back to you.  

    Is it covered by insurance?

    Whereas most health insurances (private and government plans) cover blood work prescribed by your doctor and performed in a lab, it’s doubtful that your insurance will cover an at home A1C test unless it’s a prescribed kit.

    However, you can always call your insurance company or look up your benefits and find out if your plans cover at-home kits. If it does, your insurance company may have a preferred brand or specific process for you to get your kit.



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    Fresh Fig Cake Moist & Amazing+Fresh Fig Recipes! When is Fig Season?

    By electricdiet / September 26, 2020


    Moist and delicious, Fresh Fig Cake is an all-time favorite fresh fig recipe in Holly’s cookbook, Eating Well to Fight Arthritis.  Who doesn’t like fresh easy fig recipes? You might be wondering when is fig season? The season is really from late summer to fall which is August until October, however you will find some fresh figs in early summer. Give Holly’s popular fresh fig cake moist recipe a try because her whole cookbook has a focus on anti inflammatory recipes.  This mouth-watering cake even has nutritious benefits as it is diabetic-friendly and high in potassium and fiber.

    fresh fig bundt cake

    Fresh Fig Cake
    Now, if you are one of those that turn up your nose to fresh figs, this Fresh Fig Cake will instantly change your mind.  The recipe is from Eating Well to Fight Arthritis.  I honestly couldn’t wait to include this recipe in one of my cookbooks. Actually, lots of people have asked me for fresh fig recipes.

      Servings20 servings

      Ingredients

      • 1/3cup


        canola oil

      • 1 1/2cups


        sugar

      • 1teaspoon


        vanilla extract

      • 2


        eggs

      • 1


        egg white

      • 2cups


        all-purpose flour

      • 1teaspoon


        baking soda

      • 1 1/2teaspoons


        ground cinnamon

      • 1cup


        buttermilk

      • 1cup


        coarsely chopped fresh figsstems removed

      • 1/2cup


        chopped pecans



      • Glaze

      Instructions
      1. Preheat oven 350°F. Coat Bundt pan with nonstick cooking spray.


      2. In mixing bowl, cream oil, sugar, and vanilla. Add eggs and egg white, one at a time, beating well after each addition until creamy.


      3. In small bowl, combine flour, baking soda, and cinnamon. Add flour mixture to sugar mixture, alternating with buttermilk and ending with flour. Beat after each addition.


      4. Stir in figs and pecans. Bake 40-45 minutes, until top springs back when touched. Then, let cake cool 10 minutes and then invert onto serving plate. Next, pour Glaze (recipe follows) over hot cake.

      Glaze

        Ingredients

        • 1/4cup


          sugar

        • 2teaspoons


          light corn syrup

        • 1tablespoon


          butter

        • 1/4cup


          buttermilk

        • 1/4teaspoon


          baking soda

        • 1/2teaspoon


          vanilla extract

        Instructions
        1. In small nonstick pot, combine all ingredients except vanilla and bring to boil 4 minutes over medium heat, stirring constantly. Add vanilla and pour over hot cake.

        Recipe Notes

        Per Serving: Calories 194, Protein (g) 3, Carbohydrate (g) 30, Fat (g) 7, Calories from Fat (%) 32, Saturated Fat (g) 1, Dietary Fiber (g) 1, Sugar (g) 20, Cholesterol (mg) 21, Sodium (mg) 111 Diabetic Exchanges: 2 other carbohydrates, 1 ½ fat

        Terrific Tidbit: Fresh dates may be substituted or dried fruit.

        Fresh Fig Cake
        Now, if you are one of those that turn up your nose to fresh figs, this Fresh Fig Cake will instantly change your mind.  The recipe is from Eating Well to Fight Arthritis.  I honestly couldn’t wait to include this recipe in one of my cookbooks. Actually, lots of people have asked me for fresh fig recipes.

          Servings20 servings

          Ingredients

          • 1/3cup


            canola oil

          • 1 1/2cups


            sugar

          • 1teaspoon


            vanilla extract

          • 2


            eggs

          • 1


            egg white

          • 2cups


            all-purpose flour

          • 1teaspoon


            baking soda

          • 1 1/2teaspoons


            ground cinnamon

          • 1cup


            buttermilk

          • 1cup


            coarsely chopped fresh figsstems removed

          • 1/2cup


            chopped pecans



          • Glaze

          Instructions
          1. Preheat oven 350°F. Coat Bundt pan with nonstick cooking spray.


          2. In mixing bowl, cream oil, sugar, and vanilla. Add eggs and egg white, one at a time, beating well after each addition until creamy.


          3. In small bowl, combine flour, baking soda, and cinnamon. Add flour mixture to sugar mixture, alternating with buttermilk and ending with flour. Beat after each addition.


          4. Stir in figs and pecans. Bake 40-45 minutes, until top springs back when touched. Then, let cake cool 10 minutes and then invert onto serving plate. Next, pour Glaze (recipe follows) over hot cake.

          Fig Facts To Know To Take Advantage of Fig Season:

          • A fresh fig is lusciously sweet with a slight crunch making them unique and delicious.
          • You may use dried figs or dates, however, this is one of those recipes that fresh is best.
          • They are high in potassium and fiber
          • Fresh figs are perishable so they say 90% are made into dried figs.

          Fresh Fig Recipes Make Healthy Easy Recipe

          Not only is this cake absolutely delicious but this Fig Bundt Cake recipe is a spectacular easy diabetic recipe. Remember, there’s no magical diabetic diet but it is the healthiest way to eat! Holly appeared with arthritis diet recipes on The 700 Club and everyone said these were their favorite to eat.

          Eating Well to Fight Arthritis cookbook, has a “D” that highlights diabetic-friendly recipes throughout the book. You will be surprised by how many of your favorite recipes will also be easy diabetic recipes too.  With Team Holly’s frecipes, eating healthy is made easy and fun for you! So, if you are looking for a diabetic diet, this book makes a great choice besides giving you great recipes for an anti inflammatory diet!

          fresh fig cake for fig season with fresh fig recipes for Fig Bundt Cake

          Does Your Bundt Cake Stick in the Pan? Nonstick Bundt Cake Pans Make A Difference

          With a new nonstick Bundt pan it will make such a difference in making sure your cake comes out of the pan without sticking. If you use an old pan and get aggravated when your cake gets stuck it is time for an upgrade! However, Holly always said those were the pieces of cake she got to taste and eat ahead of time – ha!

          You will like this pan but any nonstick Bundt pan works. Also, check out the different shaped holiday Bundt pans.  You’ll make quite the dessert statement.

          More Easy Fig Recipes: Incredible and Delicious Fig Pizza

          Do you like pizza? You may be thinking pizza and figs don’t go together.  Yes, they do and especially during fig season! You will look forward to making this Fig, Caramelized Onion, Prosciutto and Goat Cheese Pizza in Holly’s cookbook, Too Hot in the KitchenThis is another one of those absolutely delicious fresh fig recipes.  Honestly, you must give this delicious fig pizza a try and especially if you enjoy the savory and sweet combination. We are familiar with a fresh fig appetizer with prosciutto and goat cheese however, this pizza has the same fabulous flavors and then you have a healthy fig pizza recipe.

          Where To Find Fresh Figs  for Fresh Fig Recipes

          Fresh make a difference in this cake recipe.  If you have a Trader Joe’s in your area you’ll love these black mission figs if you can’t find fresh at your store. Take advantage of fresh figs in your local store during the season.

          Also, did you know that figs are considered an aphrodisiac? Considered a symbol of fertility and revered as an aphrodisiac, turn pizza into an alluring palate pleasing masterpiece. Just saying!  Maybe another good reason to eat figs!

          How To Can Whole Figs? Get Fresh Fig Recipes During Fig Season

          If you are interested in canning whole figs, check out this blog. According to this great blog on canning whole figs, it is an easy process of water bath canning the fruit in syrup.  Find out how to can whole figs and what to do with them after they are canned. This modern homestead site also features Holly’s famous Fresh Fig Cake on their blog so they know about delicious and easy fig recipes.

          Get All of Holly’s Healthy Easy Cookbooks

          The post Fresh Fig Cake Moist & Amazing+Fresh Fig Recipes! When is Fig Season? appeared first on The Healthy Cooking Blog.



          Sell Unused Diabetic Strips Today!

          3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism

          By electricdiet / September 24, 2020


          Abstract

          Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB–forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.

          Introduction

          Type 2 diabetes is characterized by elevated circulating glucose and HbA1c, insulin resistance, dyslipidemia, and increased body fat mass, especially in the intra-abdominal region (1,2). Risk factors for type 2 diabetes include excessive caloric intake, central obesity with increased waist-to-hip ratio, sedentary lifestyle, increasing age, and multiple genetic factors (3,4). The insulin resistance and dyslipidemia associated with type 2 diabetes involve increased circulating triacylglycerols (TAG) and reduced HDL cholesterol (HDL-C). As a result, TAG/HDL-C ratio can serve as a surrogate measure of insulin resistance (5). Several studies have shown a strong association between insulin resistance and increased concentrations of circulating branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) (6,7), also after controlling for age, BMI, sex, and race, although particular associations were observed for nonobese people and males with type 2 diabetes (8). Elevation of these essential amino acids in obesity and insulin resistance reflects, at least partly, reduced BCAA catabolism in adipose tissue, involving decreased expression and/or activity of BCAA catabolic enzymes (917). People with obesity exhibit reduced catabolism of BCAAs in visceral and subcutaneous adipose tissue, which is normalized after bariatric surgery (18). BCAAs provide carbon for de novo lipogenesis in adipocytes (19,20). Furthermore, it was recently demonstrated that cold exposure increases BCAA transport into mitochondria of brown adipocytes, augmenting thermogenesis concomitant with decreased circulating BCAA levels and improved whole-body energy homeostasis (13). These data underscore the importance of BCAA catabolism in both white adipose tissue (WAT) and brown adipose tissue (BAT), with implications for type 2 diabetes, but the mechanisms underlying these changes are not fully understood.

          Diabetes is not only associated with increased circulating BCAAs but also with circulating levels of the valine degradation product 3-hydroxyisobutyrate (3-HIB), a carboxylic acid. 3-HIB was first linked to diabetes in 1989, when higher plasma concentrations of 3-HIB were reported in individuals with type 1 diabetes, especially after fasting, with 3-HIB concentrations ranging from 20 to 100 μmol/L (21). More recently, studies have linked elevated circulating levels of 3-HIB to insulin resistance and risk of incident type 2 diabetes and gestational diabetes mellitus (2225). In contrast to CoA-bound catabolites from leucine and isoleucine degradation, 3-HIB-CoA is exclusively formed from valine breakdown and hydrolyzed by the rate-limiting enzyme 3-hydroxyisobutyryl-CoA hydrolase (HIBCH), allowing free 3-HIB to leave the mitochondria and enter the extracellular fluid (26). Previous studies have demonstrated that 3-HIB is released from muscle, heart, and preadipocytes (27), stimulates fatty acid uptake by acting as a paracrine factor on endothelial cells (28), and is involved in insulin signaling in myotubes (29). Importantly, mitochondrial catabolism of 3-HIB is a critical step for incorporation of valine-derived carbon into de novo synthesized fatty acids in developing adipocytes (27), and 3-HIB can also be converted into glucose (26,30).

          A previous study found no effect of altered 3-HIB levels on fatty acid uptake in adipose-derived endothelial cells (23). However, the role of 3-HIB in adipocytes, and in functionally distinct adipocyte subtypes, is unknown. In the current study, we sought to determine whether 3-HIB directly modulates the metabolic functions of white and brown adipocytes as a novel mechanism involved in the progression toward insulin resistance and type 2 diabetes.

          Research Design and Methods

          Human Cohorts

          Circulating 3-HIB was analyzed in three independent cohort studies (Table 1). The Hordaland Health Study (HUSK) is a community-based study with baseline measurements from 1997 to 1999 (http://husk.b.uib.no). Details of the study design and methodology have been described elsewhere (31,32). We analyzed blood samples, information about diabetes status, and body composition data from 4,942 participants (2,510 men and 2,432 women) who were born from 1925–1927 or 1950–1951 and living in Hordaland County, Norway. Participants were stratified into three groups (normoglycemia, hyperglycemia, and established type 2 diabetes) based on self-reported diabetes status corrected for glucose values. The hyperglycemia group consisted of people with self-reported nondiabetes and nonfasting plasma glucose values >7 mmol/L but <11.1 mmol/L. The group with diabetes comprised those with self-reported diabetes with addition of a few individuals who were reported to be free of diabetes but had nonfasting glucose >11.1 mmol/L. In two additional cohorts (Western Norway Obesity Biobank 1 and 2 [WNOB-1 and WNOB-2]), we analyzed blood samples from patients with severe obesity (BMI >35 kg/m2) who underwent Roux-en-Y gastric bypass surgery (WNOB-1) (33) or either gastric bypass or sleeve gastrectomy (WNOB-2) (34). WNOB-1 also included people without obesity undergoing elective surgeries, and WNOB-2 included samples collected 1 week after bariatric surgery. Notably, the patients consumed a reduced-energy diet in the weeks preceding surgery in WNOB-1, but not in WNOB-2. The majority of participants included from across the cohorts used no antidiabetic medications. Among the subgroup with established type 2 diabetes from HUSK (n = 201), 84 people used metformin, and 39 people used insulin. In WNOB-1 (n = 46), 7 patients undergoing bariatric surgery used metformin.

          Table 1

          Participant characteristics

          The studies were approved by the Regional Committee for Medical and Health Research Ethics, Western Norway (approval numbers 2010/502 [WNOB-1 and WNOB-2], 2010/3405 [primary adipocyte cultures], and 2015/876 [HUSK study]) and the Regional Ethical Committee in Gothenburg, Sweden (approval number Dnr 721–96 [perirenal adipose tissue]). All participants gave written informed consent.

          Adipose Tissue and Primary Human Adipocyte Cultures

          Ten pairs of perirenal WAT and BAT surgical biopsies were collected from healthy kidney donors (Table 2), as described previously (35). The biopsies were classified as BAT or WAT based on quantitative PCR (qPCR) analysis of uncoupling protein 1 and histological analysis.

          Table 2

          Human adipose tissue and cultures

          For primary human adipocyte cultures (donors 1–6, Table 2), the stromal vascular fraction was isolated from abdominal subcutaneous liposuction aspirate and differentiated as described previously (36). In addition, cells were obtained from another patient during thyroidectomy from human subcutaneous neck adipose tissue and immortalized (37).

          Mouse Adipocyte Cultures

          Preadipocytes from interscapular subcutaneous WAT and interscapular BAT depots from C57BL/6 male mice were isolated by collagenase and immortalized by incubation with simian virus 40 overnight, followed by passaging for 2–3 months. Immortalized mouse WAT and BAT, as well as 3T3-L1 mouse fibroblasts, were cultured and differentiated as described previously (38).

          Measurement of Amino Acids and Related Metabolites

          Cell culture media from undifferentiated or differentiated cells were collected before medium change every 2nd day throughout differentiation (48-h intervals). Total cell lysates from 1 million cells were collected for intracellular measurements. Indicated metabolites and amino acids were measured by gas chromatography–tandem mass spectrometry based on methylchloroformate derivatization at Bevital AS (Bergen, Norway; http://www.bevital.no) as previously described (39). Where indicated, data were normalized to cell number or protein concentration in cell lysates using the colorimetric DC Protein Assay Kit (Bio-Rad Laboratories), following the manufacturer’s Microplate Assay Protocol.

          siRNA Transfection

          Knockdown was performed using siRNA (Supplementary Table 1) or endo-RNase–prepared siRNA (EMU024211; Sigma-Aldrich). The siRNA was diluted in Opti-MEM Reduced Serum Media and TransIT-X2 transfection reagent (Mirus Bio LLC), and cells were incubated with targeting or nontargeting siRNA, according to the manufacturer’s protocols.

          Gene Expression Analysis

          RNA was collected from cultured cells using the RNeasy Mini QIAcube Kit (Qiagen), cDNA was synthesized with the High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems), and qPCR was performed using SYBR Green and a LightCycler 480, according to the manufacturers’ protocols. Gene expression was normalized to reference genes, and amplicon (mRNA) levels were estimated based on standard curves or the ΔΔ threshold cycle method. Primer sequences for qPCR are provided in Supplementary Table 2. For perirenal adipose tissue, HIBCH and HIBADH mRNA expression was extracted from a previous Affymetrix microarray experiment (Human Gene 1.0 ST) comparing perirenal WAT with or without interspersion of brown adipocytes (35).

          Western Blot Analysis

          Cultured cells were lysed in standard radioimmunoprecipitation assay buffer (Thermo Fisher Scientific) containing protease inhibitor (Roche, Sigma-Aldrich). Protein was quantified by the colorimetric DC Protein Assay Kit (Bio-Rad Laboratories) and analyzed by SDS-PAGE and immunoblotting (10 µg protein/well in 4–20% TGX gels [Bio-Rad Laboratories]). Membranes were blocked in blocking solution containing dried skimmed milk and in PBS-Tween and incubated with primary antibody against Hibch (1:200; HPA036541; Sigma-Aldrich), vinculin (1:5,000; ab18058; Abcam), and horseradish peroxidase–conjugated secondary antibody against mouse (1:7,500; 554002; BD Pharmingen) or rabbit (1:10,000, 3546; Pierce). Proteins were detected and quantified using a SuperSignal West Femto Maximum Sensitivity Substrate Kit (Thermo Fisher Scientific), Molecular Imager Gel Doc XR (Bio-Rad Laboratories), and Quantity One 1-D Analysis Software (version 4.6.5).

          Oil Red O Staining

          Cells were washed with PBS, fixed in 4% formaldehyde, and incubated overnight in fresh fixation solution. Oil Red O was imaged following additional washing with sterile water, incubation in 60% isopropanol at room temperature for 5 min, and staining with Oil Red O solution (3 g/L; Sigma-Aldrich). Lipid content was quantified spectrophotometrically after eluting intracellular Oil Red O using 100% isopropanol.

          Fatty Acid Uptake

          Cells were seeded in a black 96-well flat-bottom plate with clear bottoms, and fatty acid uptake was measured spectrophotometrically at 37°C following addition of 100 µL/well of Fatty Acid Dye Loading Solution, according to the manufacturer’s protocol (MAK156; Sigma-Aldrich). Data were normalized to cell number per well using Hoechst staining.

          Radioactive Glucose Uptake

          Cells were washed in PBS prior to 16-h incubation in medium containing 1:1 of DMEM without glucose (Gibco) and Ham’s Nutrient Mixture F12 (Thermo Fisher Scientific). Thereafter, cells were incubated for 2 h in glucose-free medium with or without treatment before insulin (10 nmol/L) was added to indicated wells. After 30 min, deoxy-D-[14C]glucose (57.7 mCi/mmol, final concentration 1.73 μmol/L; PerkinElmer) was subjected to cells for 30 min. Cells were placed on ice, washed twice, and lysed using 0.1% SDS lysis buffer. Lysates were transferred to Ultima Gold fluid cartridges (PerkinElmer), and radioactivity was measured as counts per minute using a Tri-Carb 4910TR scintillation counter (PerkinElmer). Counts were normalized to protein concentration using DC Protein Assay Kit (Bio-Rad Laboratories) as described previously. All incubations were performed at 5% CO2 and 37°C.

          Reactive Oxygen Species Generation

          Generation of reactive oxygen species (ROS) in adipocytes was quantified by using the fluorescent probe CM-H2DCFDA (Thermo Fisher Scientific). Cells were first incubated for 30 min at 37°C with 5 μmol/L probe (dissolved in DMSO and diluted in PBS) and washed twice with warm Krebs Ringer buffer. The measurement was conducted using a 96-well SpectraMax Gemini EM (Molecular Devices) plate reader at 37°C. Fluorescence (485-nm excitation, 515-nm emission) of the oxidized probe was measured once every 10 min until steady-state ROS signal was obtained. Data were normalized to cell number per well using Hoechst staining.

          Mitochondrial Respiration

          Seahorse XF Cell Mito Stress Test Assay (Agilent Technologies) was conducted following the manufacturer’s protocol. Briefly, XF96 cell culture microplates were coated (0.1% gelatin) before seeding of preadipocytes. Prior to assay, cells were washed with XF base medium supplemented with L-glutamine, glucose, and sodium pyruvate (final concentrations of 2 mmol/L, 10 mmol/L, and 2 mmol/L, respectively) and treated as indicated in figure legends (Fig. 6). Subsequently, cells were incubated for 1 h 20 min (37°C without CO2), prior to measurements of cellular respiration. Data were normalized to cell number per well using Hoechst staining.

          Statistical Analysis

          All statistical analyses were performed using the software GraphPad Prism 8 and R (version 3.6.1). Some gas chromatography-tandem mass spectrometry analyses were done in biological singlets in which five to six biological replicates were pooled. For the HUSK cohort, differences in valine and 3-HIB concentrations between groups with diabetes were modeled by multiple linear regression adjusted for age and sex. Differences between groups are reported in units of z scores obtained by standardizing the outcome variables (valine and 3-HIB). Similarly, the association between 3-HIB and established risk markers was performed as described above, with risk marker variables standardized and results reported as standardized regression coefficients. Additionally, the strength of association of 3-HIB and valine with diabetes was compared in a multivariable setting using logistic regression and stepwise selection of predictors, keeping age and sex as constant adjustment throughout. Using a combination of forward and backward selection, the final model consisted of 3-HIB, TAG, BMI, and HDL-C selected in that order. The analysis was repeated in subgroups according to sex and age, with patients with either diabetes or diabetes and hyperglycemia pooled as outcome. Association of variables in WNOB-1 was assessed by Spearman correlation adjusted for age and sex or adjusted for all included variables with correlations visualized using the function qgraph (package qgraph) in R. To assess significant differences between two groups in WNOB-1/2 and cell culture experiments, two-tailed unpaired t tests (assuming normal distribution) were performed. Ordinary one-way ANOVA (Tukey) was performed to assess significant difference for greater than two groups. Data are presented as means ± SEM or means with 95% CI (HUSK data). A significant difference was defined as P < 0.05.

          Data and Resource Availability

          The experimental data sets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. However, restrictions apply to the general availability of the human/clinical data because of our ethical approval, patient agreements, and the sensitive nature of the data. Except for potentially sensitive patient information, access to the HUSK cohort data can be applied for via https://husk-en.w.uib.no/how-to-apply-for-data-access/. No applicable resources were generated or analyzed during the current study.

          Results

          Association of Circulating 3-HIB With Hyperglycemia and Type 2 Diabetes

          To evaluate circulating 3-HIB concentrations as a marker of type 2 diabetes status, plasma 3-HIB and valine concentrations available in 4,942 people from a large population-based cross-sectional cohort were investigated (HUSK cohort, Table 1). Compared with people with normoglycemia, those with hyperglycemia (glucose >7 and <11.1 mmol/L) had higher levels of 3-HIB (z score 0.45) and valine (z score 0.33), and those with established type 2 diabetes had even higher levels (z scores of 0.87 and 0.71 for 3-HIB and valine, respectively) (Fig. 1A). These data suggest that 3-HIB is a strong marker of increasing hyperglycemia. In addition, 3-HIB correlated with surrogate measures of insulin resistance and adiposity and showed similar regression coefficients with these measures for the group with normoglycemia as for the groups with hyperglycemia and type 2 diabetes (Fig. 1B), suggesting a potential role of 3-HIB in diabetes development. Comparing the strength of association of valine and 3-HIB with diabetes using logistic regression, the effect estimate for 3-HIB (adjusted for age and sex) was stronger and less affected by multiple adjustment than the other predictors (BMI, TAG, HDL-C, and valine), and, notably, in no case was valine present in the final model. With all predictors retained in the model (diabetes as outcome and all subgroups combined), the β coefficients were as follows: 3-HIB, 0.68 (0.50, 0.87); TAG, 0.24 (0.05, 0.44); BMI, 0.27 (0.10, 0.43); HDL-C, −0.18 (−0.38, 0.01); and valine, 0.13 (−0.08, 0.34).

          Figure 1
          Figure 1

          Circulating 3-HIB is associated with type 2 diabetes and measures of insulin resistance and adiposity in the HUSK cohort. A: Plasma concentrations (adjusted geometric mean ± 95% CI) of 3-HIB and valine in the groups with normoglycemia (n = 4,537), hyperglycemia (n = 204), and established type 2 diabetes (n = 201). The group with hyperglycemia consisted of people with glucose values >7 mmol/L but <11.1 mmol/L. The group with diabetes was based on self-reported diabetes with the addition of a few individuals with nonfasting glucose >11.1 mmol/L. B: Associations for plasma 3-HIB and measures of insulin resistance and adiposity in multivariate models adjusted for age and sex in the groups with normoglycemia (n = 4,761) and hyperglycemia/diabetes combined (n = 405). The combination of the latter groups gave a similar result as for the groups individually but increased statistical power. The group with hyperglycemia/diabetes included participants with self-reported type 2 diabetes and those with nonfasting glucose levels >7 mmol/L. Data are shown as estimates with 95% CI. WHR, waist-to-hip ratio.

          Association of Circulating 3-HIB With Obesity and Measures of Insulin Resistance

          To corroborate the relationship between circulating 3-HIB and insulin resistance, the association between these measures was investigated in people with different degrees of adiposity and insulin resistance (WNOB-1 cohort, Table 1). Although 3-HIB and valine showed similar positive correlations with HOMA2 of insulin resistance (HOMA2-IR) and insulin C-peptide and an inverse correlation with HDL-C, 3-HIB showed stronger positive correlations with BMI and glucose, while valine showed stronger correlations with TAG and TAG/HDL-C (Fig. 2A). Notably, after multiple adjustments, 3-HIB demonstrated both a positive association with HOMA2-IR and negative associations with TAG and HOMA2 of β-cell function, while valine showed weaker associations with the same variables (Fig. 2B). The link among 3-HIB, obesity, and insulin resistance was further supported by a marked decrease in circulating 3-HIB 1 year after bariatric surgery compared with presurgical values (WNOB-1 cohort), similar to the BCAAs (Fig. 2C and Supplementary Fig. 1B).

          Figure 2
          Figure 2

          Circulating 3-HIB is associated with obesity-related insulin resistance and shows dynamic changes after bariatric surgery. A and B: Graphical representation of Spearman correlations for serum 3-HIB and valine concentrations and measures related to insulin resistance in 85 people ranging in BMI from 18 to 57 kg/m2 (WNOB-1 cohort). A: Correlations are significant for Spearman ρ <−0.22 and >0.22 (indicated by dashed lines). B: The correlations were adjusted for all variables shown in addition to age and sex. Green and red lines indicate positive and negative correlations, respectively, and line thickness the strength of correlation. C: Serum concentrations of 3-HIB and valine in patients with obesity pre– and 1 year post–bariatric surgery. Data are presented as mean ± SEM (t test) (WNOB-1 cohort). D: Individual serum concentrations of 3-HIB and valine in patients with obesity before, 1 week post–, and 1 year post–bariatric surgery (Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy) (WNOB-2 cohort). The black line indicates mean levels and gray lines individual levels. H2-B, HOMA2 of β-cell function; H2-IR, HOMA2-IR; Pre, before bariatric surgery; Val, Valine. **P < 0.01; ***P < 0.001.

          Improvement in insulin resistance following bariatric surgery can occur within days, at least partially independent of weight loss (34). Circulating 3-HIB levels before and 1 week after bariatric surgery were also measured, as well as after 1 year (WNOB-2 cohort). Like the WNOB-1 cohort, there was a decrease in circulating 3-HIB 1 year after surgery. By contrast, the samples collected 1 week after bariatric surgery showed increased levels of 3-HIB and BCAAs (Fig. 2D and Supplementary Fig. 1C).

          Adipocyte Release of 3-HIB During Adipogenic Differentiation and Lipid Accumulation

          We investigated whether 3-HIB plays a regulatory role in adipose tissue function by analyzing metabolite fluxes in differentiating mouse 3T3-L1 and primary human adipocytes. 3-HIB efflux increased markedly during differentiation of both 3T3-L1 and primary human adipocytes, with a rebound in the later stages (Fig. 3A and B and Supplementary Fig. 2A and B). In 3T3-L1 cells, this change in 3-HIB corresponded to decreased BCAAs and increased glutamine in the culture medium throughout differentiation (Fig. 3A and Supplementary Fig. 2A and B). Although differentiating primary human adipocytes showed less fluctuation in extracellular BCAA concentrations than the 3T3-L1 cells (Fig. 2B), immortalized human adipocytes showed a clear increase in BCAA consumption accompanied by increased 3-HIB efflux, similar to what was observed in 3T3-L1 cells (Supplementary Fig. 2C and D). 3T3-L1 cells transiently accumulated intracellular 3-HIB in middifferentiation (days 2–4), but not in later stages (days 7–9) (Supplementary Fig. 2C). The changes in intracellular 3-HIB levels did not correspond with BCAA levels. As in 3T3-L1 cells, intracellular 3-HIB levels were unchanged in the mature immortalized primary human adipocytes, despite increased intracellular BCAA levels (Supplementary Fig. 2D). Taken together, both mouse and human adipocytes showed increased 3-HIB release during adipogenic differentiation, which often occurred in the absence of any change in BCAAs.

          Figure 3
          Figure 3

          Altered BCAA consumption and intracellular lipid accumulation. Changes in concentrations of amino acids and 3-HIB in culture medium throughout adipogenic differentiation in 3T3-L1 cells (A) (n = 3) and primary human adipocytes (B) (donors 1 and 2, n = 4). Mean ± SEM for absolute values are shown. C and D: Relative mRNA levels of key BCAA catabolic enzymes during adipogenic differentiation were measured in 3T3-L1 (C) (n = 3) and primary human adipocytes (D) (n = 9–12, pooled data for cultures from donors 3–6) using qPCR and calculated relative to expression of Rps13 or IPO8. One-way ANOVA with Dunnett test (median value of day 0 [C] or 2 [D] as control column) performed and presented as mean ± SEM. E: Protein levels of HIBCH (left) and the quantitative values of HIBCH relative to α-vinculin (α-VCL) (right) in immortalized primary human adipocyte cultures obtained from subcutaneous WAT. Antibody control including HIBCH knockdown to demonstrate specificity of the antibody shown in bottom panel. FH: siRNA knockdown (final concentration of 25 nmol/L siRNA/well) was performed at day 2 and repeated every 48 h throughout differentiation. F: Effect of Hibch siRNA knockdown on mRNA level in 3T3-L1 (n = 3). G: Protein levels of HIBCH (left) and the quantitative values of HIBCH relative to α-VCL (right) in 3T3-L1 (n = 3). H: Oil Red O–stained 3T3-L1 adipocytes differentiated for 6 days, with and without siRNA-mediated knockdown of Hibch (n = 6). The results are representative of three individual experiments. I: Relative values of extracellular (medium) 3-HIB levels at day 6 during Hibch siRNA knockdown in 3T3-L1 (n = 6). Relative values are shown and normalized to control. The results are presented as mean ± SEM. Nontargeting siRNA was used as control to Hibch knockdown. *P < 0.05; **P < 0.01; ***P < 0.001. Undiff, undifferentiated.

          We next evaluated if the 3-HIB release during differentiation corresponded with changes in BCAA catabolic enzyme levels, with a focus on HIBCH and HIBADH immediately upstream and downstream of 3-HIB. Using qPCR, we found a gradual increase in mRNA levels of BCAA catabolic enzymes during differentiation in both 3T3-L1 (Fig. 3C) and in primary and immortalized human adipocytes (Fig. 3D and Supplementary Fig. 2G and H). Western blot analysis also demonstrated two- to threefold higher HIBCH protein level in late adipogenesis, corresponding closely to mRNA levels (Supplementary Fig. 2I and J). The HIBCH protein level was also increased in immortalized human white adipocytes when comparing fully differentiated to undifferentiated cells (Fig. 3E). Conversely, siRNA knockdown of HIBCH in differentiating 3T3-L1 cells, which reduced Hibch mRNA level by 80% and HIBCH protein levels by 40% (Fig. 3F and G), decreased lipid accumulation by ∼25% (Fig. 3H), and reduced 3-HIB efflux from the cells by 20% (Fig. 3I).

          BCAA Metabolism and 3-HIB in White and Brown Adipocytes

          Reports have demonstrated metabolic effects of altered BCAA consumption in WAT and BAT (1315,40), but to our knowledge, a direct comparison of WAT and BAT has not been performed. We found that, in C57BL/6 mice, BAT showed several-fold higher mRNA expression of key BCAA catabolic enzymes compared with WAT (e.g., Bckdha, Hibch, and Hibadh) (Fig. 4A). We also observed significantly higher mRNA levels in human perirenal adipose tissue containing brown adipocytes compared with perirenal adipose tissue containing only WAT (Fig. 4B). Similarly, in immortalized primary cultures of differentiated white and brown mouse adipocytes, with similar lipid accumulation (Fig. 4C), brown adipocytes showed considerably higher mRNA expression levels of key BCAA catabolic enzymes, with two- to fivefold higher mRNA levels in differentiated brown compared with differentiated white adipocyte cultures (Fig. 4D). As expected, expression of mature adipocyte markers (Pparg2, Glut4, and the uncoupling marker Ucp1) was substantially higher in brown adipocytes (Fig. 4D). Western blot showed increased HIBCH protein in parallel with the increased Hibch mRNA expression in both cell types, with a stronger induction upon adipogenic differentiation in brown adipocytes (Fig. 4E). Despite these differences in enzyme expression, the white and brown adipocytes released similar amounts of 3-HIB into the culture medium upon adipogenic differentiation and had similar intracellular 3-HIB levels (Fig. 4F). However, while both white and brown adipocytes showed similarly reduced extracellular BCAA levels after differentiation (indicating increased consumption), intracellular BCAA levels were higher in brown compared with white preadipocytes (Supplementary Fig. 2K).

          Figure 4
          Figure 4

          Comparison of white and brown adipocytes shows differences in BCAA metabolism. A: Relative mRNA levels of Bckdha, Hibch, and Hibadh in WAT and BAT dissected from C57BL/6 mice (mWAT and mBAT) (n = 10–12). B: Absolute values of mRNA levels (signal intensity) of HIBCH and HIBADH from array analysis of perirenal human adipocytes from WAT and BAT surgical biopsies (from healthy kidney donors) (hWAT and hBAT) (n = 10). C: Representative images of Oil Red O lipid stained adipocytes (left) and quantification of lipid accumulation (right) (n = 3) in immortalized WAT and BAT obtained from C57BL/6 mice. D: Relative mRNA levels of genes encoding BCAA catabolic enzymes and genes involved in differentiation, adipocyte maturation, and browning (n = 4). Expression was calculated relative to values in undifferentiated (Undiff) WAT cultures. The results are presented as mean ± SEM. E: Western blots showing protein levels of HIBCH (left) and the quantitative values of HIBCH relative to α-vinculin (α-VCL) (right). Relative values normalized to control (nontargeting siRNA) for each cell type are presented (n = 2). F: Extracellular (cell culture medium, 48-h consumption) and intracellular levels of 3-HIB (relative to protein) in undifferentiated controls and cells differentiated for 8 days (n = 1/time point; samples originating from six 15-cm dishes pooled together). *P < 0.05; **P < 0.01; ***P < 0.001. Pre-diff, predifferentiation.

          We further examined how altered levels of HIBCH might affect adipocyte metabolic functions by performing knockdown experiments in primary white and brown adipocytes from mice followed by measurements of fatty acid and glucose uptake and mitochondrial oxygen consumption. In addition, we measured ROS generation, which is linked to altered mitochondrial respiration and impaired adipocyte function (41). HIBCH knockdown, with 90–95% reduction of mRNA and 30–40% of protein (Fig. 5A and B), decreased lipid accumulation by 25–40% in both white and brown adipocytes (Fig. 5C), concomitant with 45–50% reduced 3-HIB efflux from the cells (Fig. 5D).

          Figure 5
          Figure 5

          Hibch knockdown reduces lipid accumulation and 3-HIB efflux. AD: Knockdown (final concentration of 25 nmol/L siRNA/well) was performed on day 2 and repeated every 48 h during differentiation. Nontargeting siRNA was used as control to Hibch knockdown. Effect of Hibch siRNA knockdown on mRNA level (B) (n = 3) and on protein levels of HIBCH (C) (left) (n = 3) in WAT and BAT and the quantitative values of HIBCH relative to α-vinculin (α-VCL) (right). C: Mature WAT and BAT adipocytes subjected to Oil Red O staining on day 6 show reduced lipid accumulation compared with control after knockdown of Hibch (n = 6). These results are representative of three independent experiments with siRNA or endo-RNase–prepared siRNA. D: Relative values of extracellular (medium) 3-HIB levels at days 4 and 6 during Hibch knockdown in WAT and BAT (n = 6). Relative values are shown and normalized to control for each cell type. The results are presented as mean ± SEM. ***P < 0.001.

          Conversely, addition of 3-HIB using both physiological (25–100 μmol/L) and supraphysiological (10 mmol/L) concentrations to the cell cultures increased fatty acid uptake in white adipocytes by 15–25% (Fig. 6A). Short-term (3-h) treatment with 10 mmol/L 3-HIB also counteracted insulin-stimulated glucose uptake in both adipocyte cell types, but 100 μmol/L 3-HIB had no significant effect (Fig. 6B). In contrast, longer-term (24-h) treatment with 3-HIB increased insulin-stimulated glucose uptake in both cell types, although no effect was seen with lower doses of 3-HIB in brown adipocytes. The 24-h high-dose treatment also tended to increase basal glucose uptake (Fig. 6B). Finally, we observed that the addition of 3-HIB acutely decreased maximal mitochondrial respiration, spare respiratory capacity, and ROS generation by 20–50% in white adipocytes, while in brown adipocytes, these measures increased by 10–35% primarily at the high dose (Fig. 6C and D). The effects on mitochondrial respiration were replicated in cells supplemented with 3-HIB for 2 days (Supplementary Fig. 3). Taken together, these data demonstrate a regulatory role for 3-HIB in core adipocyte functions.

          Figure 6
          Figure 6

          3-HIB affects uptake of fatty acids and glucose, mitochondrial respiration, and ROS generation in WAT and BAT adipocytes. A: Fatty acid uptake (shown by relative fluorescence units [RFU]) at day 6 in differentiating WAT and BAT cells (n = 11–12). 3-HIB (final concentrations of 25–100 μmol/L and 10 mmol/L) was added minutes (∼5 min) before starting the measurements. B: Glucose uptake (shown by counts per minute [cpm]/μg protein) at day 6 in differentiating WAT and BAT cells (n = 5–6) with (+) or without (−) insulin (ordinary one-way ANOVA). 3-HIB (final concentrations of 25–100 μmol/L and 10 mmol/L) was added to the cells 3 h or 24 h before measurements. Water was used as control to 3-HIB treatment. C: Seahorse XF Cell Mito Stress Assay was performed following the manufacturer’s Mito Stress protocol using the Seahorse XFe96 Analyzer to assess the mitochondrial respiration in WAT and BAT (n = 10–12) at day 5 in differentiation. 3-HIB treatment (final concentrations of 100 μmol/L and 10 mmol/L) was added 2 h before the first oxygen consumption rate (OCR) measurements in the Seahorse XFe96 Analyzer. Measurements of OCR were performed during injection of the mitochondrial-modulating compounds oligomycin, carbonyl cyanide m-chlorophenyl hydrazine (CCCP), antimycin A (Antim.), and rotenone (Rot.) (final 1 μmol/L of each, as indicated at the top in the top left panel). Outliers were removed based on a whisker Tukey test of the OCR data for each time point in each well. Basal respiration, ATP production, maximal respiration, spare capacity, and uncoupling were calculated for each well based on the OCR measurements, in accordance with the protocol from the manufacturer (Agilent Technologies). D: Short-term effect of 3-HIB addition on the production of ROS at day 6 in differentiating WAT and BAT cells (n = 11). 3-HIB (final concentrations of 25 μmol/L, 100 μmol/L, and 10 mmol/L) was added 5 min before starting the measurements. A, C, and D: Data were normalized to cell counts per well by Hoechst staining. *P < 0.05; **P < 0.01; ***P < 0.001. Ctrl w/o, control without.

          Discussion

          In the current study, we found elevated plasma 3-HIB concentrations mirroring the degree of insulin resistance, with the highest levels observed in established type 2 diabetes. Additionally, we provide novel mechanistic data implicating 3-HIB as an adipocyte-derived autocrine/paracrine and possibly endocrine signaling molecule, demonstrating stimulatory effects on adipocyte lipid accumulation, modulation of insulin-stimulated glucose uptake, and differential effects on mitochondrial respiration dependent on adipocyte subtype. A marked decrease in plasma 3-HIB 1 year after bariatric surgery and weight loss further supports the clinical relevance of the mechanistic data.

          White and brown adipocyte functions are critically involved in the regulation of circulating BCAA levels and systemic insulin resistance (1315,17), but the underlying mechanisms are not fully understood. An important discovery in our study is the effect of increased 3-HIB on fatty acid uptake and insulin-stimulated glucose uptake directly in adipocytes. Earlier studies suggested that 3-HIB promotes insulin resistance in skeletal muscle by increasing fatty acid uptake from endothelial cells (28), while no 3-HIB–mediated fatty acid uptake was found in adipose-derived microvascular endothelial cells (23). In adipocytes, we observed a time-dependent regulation of insulin-stimulated glucose uptake by 3-HIB, with a decrease in the short term and an increase in the longer term. While the physiological relevance of this dynamic regulation is unclear, the stimulatory effect of chronically elevated 3-HIB on adipocyte glucose uptake is consistent with increased fat storage (e.g., by providing pyruvate for TAG synthesis) and the role of adipocyte insulin signaling in promoting obesity and glucose intolerance (42). Notably, short-term 3-HIB treatment increased fatty acid uptake, while insulin-stimulated glucose uptake decreased, indicating that sources other than glucose (e.g., pyruvate) contributed to glyceroneogenesis, as seen with fasting and high-carbohydrate diets (43).

          Interestingly, we found that addition of 3-HIB decreased mitochondrial respiratory capacity in white adipocytes, a metabolic change associated with obesity in different mouse models (44). In contrast, brown adipocytes responded to 3-HIB addition by increasing mitochondrial respiratory capacity and ROS generation. Our data suggest that this difference is mediated by substantially higher expression of BCAA catabolic enzymes in brown adipocytes and consequent differences in valine degradation and anaplerosis. 3-HIB can be channeled toward the tricarboxylic acid cycle via methylmalonic acid or toward lipogenesis (27). Consistently, altered BCAA catabolism has been shown to limit mitochondrial respiratory capacity (11). Thus, our findings indicate that differential enzyme expression and 3-HIB utilization in white and brown adipocytes may determine the channeling of 3-HIB toward fatty acid synthesis or oxidative phosphorylation and thermogenesis.

          Importantly, we demonstrate that HIBCH knockdown is sufficient to reduce 3-HIB efflux as well as lipid accumulation in white and brown adipocytes, supporting an independent role for the valine–3-HIB catabolic pathway in lipid accumulation in both adipocyte subtypes. Differentiation of white adipocytes was previously shown to involve a switch of substrate utilization from glucose and glutamine to BCAAs (7,19), and our enzyme expression data suggest this also occurs in brown adipocytes. A recent study showed that decreased BCAA catabolism specifically in BAT resulted in diet-induced obesity and glucose intolerance (13) and that BCAA catabolism in BAT regulates systemic BCAA clearance by increasing BCAA utilization upon cold exposure (13). Conceivably, 3-HIB may play a role in this metabolic regulation, in part by affecting fatty acid uptake, mitochondrial respiration, and ROS generation in brown as well as white adipocytes.

          When comparing people with hyperglycemia and type 2 diabetes to those with normoglycemia in the large population-based HUSK cohort, we observed a greater difference in circulating concentrations of 3-HIB than in the precursor valine. Moreover, multiadjusted logistic regression analysis showed that 3-HIB, but not valine, was independently associated with type 2 diabetes in a multivariable setting. This indicates, as recently suggested (25), that measurement of circulating 3-HIB may capture altered insulin resistance–related cellular processes more directly than circulating BCAAs—in this case, valine. Interestingly, we also found that 3-HIB increased transiently 1 week after bariatric surgery, a treatment that acutely increases insulin sensitivity (34). This suggests that circulating 3-HIB may also reflect a transient metabolic adaptation during reduced food intake. A previous study reported higher plasma concentrations of 3-HIB in overnight-fasted people with type 1 diabetes compared with fasted subjects without diabetes (21). In addition, people without diabetes who fasted for 72 h had even higher levels than overnight-fasted people, indicating that 3-HIB levels rise both in the state of type 1 diabetes and upon prolonged fasting (21). Of note, elevated plasma 3-HIB in patients with liver cirrhosis, another state of insulin resistance, coincides with increased catabolism of amino acids and lipids due to a lack of cellular glucose supply (45).

          It is also worth noting that skeletal muscle myocytes were found to increase the release of 3-HIB following overexpression of peroxisome proliferator–activated receptor γ coactivator-1α, a transcriptional coactivator that plays a central role in the cellular response to fasting and exercise (28). The authors proposed that 3-HIB, at least partly, mediates insulin resistance by upregulating endothelial fatty acid uptake within skeletal muscle. Conversely, when glucose and insulin increase during hyperinsulinemic-euglycemic clamp, circulating 3-HIB was found to decrease rapidly (22). However, protein intake during the clamp, which decreased insulin-stimulated glucose disposal, prevented the decrease in 3-HIB, supporting a link between 3-HIB and acute changes in nutrient supply and insulin resistance (22). Our mechanistic data indicate that 3-HIB participates in the dynamic, homeostatic regulation of cellular insulin signaling and nutrient metabolism, further supported by the inverse correlation with TAG after adjusting for other covariates. Overall, while 3-HIB responds acutely to different nutritional states, elevated circulating 3-HIB concentrations may largely reflect fat storage, evidenced by strong positive correlations with BMI and waist-to-hip ratio and marked reductions in 3-HIB following surgery-induced fat loss. Of note, because 3-HIB followed a similar pattern as valine in our cohorts, it is also possible that changes in 3-HIB levels at least partly depended on altered valine concentrations.

          Muscle, heart, and preadipocytes (27), as well as white and brown adipocytes, may all release 3-HIB, but the main sources of increased circulating 3-HIB in obesity and insulin resistance are unknown. A previous study suggested that adipose tissue may contribute more to circulating BCAAs than muscle (17). Genetic manipulation of BCAA enzymes in both adipose tissue and skeletal muscle has been shown to affect circulating BCAA levels as well as cell differentiation and lipid accumulation (10,19,28). In light of our findings that adipocytes release 3-HIB during development and increasing lipid storage and considering the relatively large adipose tissue mass among individuals with obesity, insulin resistance, and type 2 diabetes, it is possible that adipocytes may contribute substantially to elevated circulating 3-HIB in these conditions. However, caution is merited in this case because people with obesity and insulin resistance show evidence of reduced BCAA catabolism in adipose tissue (10,11,18,46), which may limit 3-HIB generation from valine in adipocytes. Although reduced BCAA activity in unison with elevated circulating BCAA levels has been consistently observed in obesity-related conditions, reported circulating 3-HIB concentrations are ∼10-fold lower than that of valine, and thus, any pronounced elevation in 3-HIB levels may be more readily identified.

          Our study has limitations. Study participants comprised a relatively homogenous population from Western Norway, and the generalizability to other populations and ethnicities needs further investigation. Sex differences found to influence the link between BCAAs and metabolic risk factors (8,47) should also be explored for 3-HIB, even though adjustment for sex did not notably influence the results of our analyses. Furthermore, it remains to be determined if adipocytes contribute to circulating 3-HIB in vivo and how this might influence whole-body energy metabolism and insulin sensitivity.

          In conclusion, we report a novel role for 3-HIB in white and brown adipocyte metabolism, not only as an indicator of mitochondrial valine catabolism, but also as a potentially important metabolic regulator of adipocyte nutrient uptake and mitochondrial respiration. Our results raise the possibility that 3-HIB serves as an adipocyte-derived signaling molecule that contributes to metabolic cross talk between different adipocyte subtypes as well as other tissues.

          Article Information

          Acknowledgments. The authors thank the participants who contributed data; Linn Skartveit and Margit Solsvik at the Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital (Bergen, Norway) and Department of Clinical Science, University of Bergen (Bergen, Norway) for expert technical assistance; and Arne-Christian Mohn, Lillian Skumsnes, Hans-Jørgen Nielsen, Tone Flølo, and other staff members at Haugesund Hospital (Haugesund, Norway) and Voss Hospital (Bergen, Norway) and Christian Busch at Plastikkirurg1 (Bergen, Norway) for collecting samples.

          Funding. The study was supported by Norges Forskningsråd (263124/F20), the Diabetesforbundet (Norwegian Diabetes Association), the Western Norway Health Authority, the Bergen Medical Research Foundation, and the Trond Mohn Foundation (Bergen, Norway).

          Duality of Interest. M.K.S. is currently employed by Amgen AB. No other potential conflicts of interest relevant to this article were reported.

          Author Contributions. S.N.D. conceived the study with input from M.S.N., R.Å.J., A.U., A.Mc., and P.M.U. The clinical cohort studies were designed and organized by P.-A.S., M.K.S., B.G.N., O.A.G., G.S.T., G.M., and S.N.D. The immortalized white and brown adipocyte cultures were developed by M.S.N. and S.N.D. supported by C.R.K. A.U. and A.Mc. contributed to metabolomics and statistical analyses. R.Å.J. and A.Ma. helped carry out experiments. M.S.N., R.Å.J., and S.N.D. designed experiments, researched data, and wrote the manuscript. All authors reviewed, edited, and approved the final version of the manuscript. S.N.D. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

          Prior Presentation. This study was presented at the Norwegian Association for Obesity Research annual meeting, Bodø, Norway, 18–19 October 2018; the Norwegian Association for Obesity Research annual meeting, Oslo, Norway, 17–18 October 2019; and the 26th European Congress on Obesity, Glasgow, U.K., 28 April–1 May 2019.

          • Received November 26, 2019.
          • Accepted June 16, 2020.



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          Low Sodium No Soak Beans (Instant Pot)

          By electricdiet / September 22, 2020


          These low sodium no soak beans are the easiest, fastest way to make your own beans right at home! Once you try them, you may never buy canned beans again.

          A spoonful of Low Sodium No Soak Beans made in the Instant Pot

          Did you know that beans are a great food to help you manage diabetes?

          While they do contain carbs, they’re also packed with fiber, which can help slow the absorption of sugar. Plus they’re a great way to add texture to any meal.

          Unfortunately, canned beans are notoriously high in sodium. They also contain preservatives and other fillers you may not want to be ingesting.

          So ditch the canned stuff and make your own low sodium, no soak beans right at home! This Instant Pot method is definitely the easiest, fastest way I’ve ever found.

          You’ll be amazed at how much better homemade beans taste. They’re also more cost-effective than buying the canned version AND healthier for you! Really, what’s not to love?

          How to make low sodium no soak beans

          Ready to see just how easy it is to cook your own beans right at home?

          Step 1: Combine 1 pound of dried beans with 5 cups of broth in the electric pressure cooker.

          Step 2: Drizzle 1 tablespoon of olive oil on top.

          Step 3: Close and lock the lid of the pressure cooker. Set the valve to “Sealing.”

          Step 4: Set the pressure cooker to HIGH pressure. Set the timer to 25 minutes for black beans; 30 minutes for garbanzo, pinto, navy, or great northern beans; or 40 for cannellini beans.

          Step 5: Once the timer is done, hit CANCEL. Let the pressure cooker sit for 20 minutes to allow it to naturally release.

          Step 6: After 20 minutes, turn the valve to “Venting” to release any remaining pressure.

          Step 7: Once the pressure pin drops, unlock and remove the lid.

          That’s it! Depending on which beans you’re cooking, the entire process should only take about an hour to an hour and fifteen minutes. It’s definitely the fastest way to cook beans right at home.

          Ways to use beans

          Now that you have delicious home-cooked beans ready to go, how are you going to use them?

          In case you need some inspiration, here are a few of my favorite recipes that are so much better with homemade beans!

          Of course, you can always add beans to salads and soups. Or you can simply enjoy them alongside a lean and healthy protein for a well-balanced meal!

          Storage

          This recipe will give you 6 cups of cooked beans. You can store them covered in the refrigerator for up to a week.

          However, if you don’t think you’ll eat that many beans that quickly, these are great to store in the freezer! I recommend freezing them in 1½ cup portions, which is roughly equivalent to a 15-ounce can of beans.

          Then, once you have a recipe that calls for beans, just take a serving out of the freezer to thaw and enjoy!

          Other popular homemade recipes

          Food made from scratch is always going to be healthier than what you can buy from the store. You can control ingredients like salt or sugar, plus you don’t have to deal with any added fillers or preservatives!

          And in a lot of cases, it’s easier than you think. Here are a few of my favorite foods to make at home instead of buying from the store:

          When you’ve tried this method for cooking beans, please don’t forget to let me know how you liked it and add a rating in the comments below!

          Recipe Card

          Low-Sodium No-Soak Beans (Instant Pot)

          Low Sodium No Soak Beans (Instant Pot)

          These low sodium no soak beans are the easiest, fastest way to make your own beans right at home! Once you try them, you may never buy canned beans again.

          Prep Time:5 minutes

          Cook Time:40 minutes

          Pressure Up/Down:35 minutes

          Total Time:1 hour 20 minutes

          Author:Shelby Kinnaird

          Servings:6

          Instructions

          • Combine 1 pound of dried beans with 5 cups of broth in the electric pressure cooker.

          • Drizzle 1 tablespoon of olive oil on top.

          • Close and lock the lid of the pressure cooker. Set the valve to “Sealing.”

          • Set the pressure cooker to HIGH pressure. Set the timer to 25 minutes for black beans; 30 minutes for garbanzo, pinto, navy, or great northern beans; or 40 for cannellini beans.

          • Once the timer is done, hit CANCEL. Let the pressure cooker sit for 20 minutes to allow it to naturally release.

          • After 20 minutes, turn the valve to “Venting” to release any remaining pressure.

          • Once the pressure pin drops, unlock and remove the lid.

          Recipe Notes

          This recipe is for 6 servings of beans. Each serving is half a cup of cooked beans.
          Beans can be stored covered in the refrigerator for up to a week.
          You can also freeze cooked beans for longer storage. Separate them into 1½ cup portions and use them whenever a recipe calls for a 15-ounce can of beans.

          Nutrition Info Per Serving

          Nutrition Facts

          Low Sodium No Soak Beans (Instant Pot)

          Amount Per Serving (0.5 cups)

          Calories 157
          Calories from Fat 19

          % Daily Value*

          Fat 2.1g3%

          Saturated Fat 0.4g3%

          Trans Fat 0g

          Polyunsaturated Fat 0.3g

          Monounsaturated Fat 1.3g

          Cholesterol 0mg0%

          Sodium 0mg0%

          Potassium 0mg0%

          Carbohydrates 24g8%

          Fiber 12.4g52%

          Sugar 0.4g0%

          Protein 8.3g17%

          Net carbs 11.6g

          * Percent Daily Values are based on a 2000 calorie diet.

          Course: Side Dish, Vegan, Vegetarian

          Cuisine: American, Gluten-free

          Diet: Diabetic

          Keyword: beans, dried beans, instant pot, no-soak beans, salt-free beans



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          Skinny Gluten Free Pizza Dough

          By electricdiet / September 20, 2020


          I MADE SKINNY GLUTEN FREE PIZZA!

          In 2016 I made a gluten free pizza recipe for a friend who had a gluten intolerance.  

          This was before I made the skinny pizza dough, and well, lots of people wanted a gluten free skinny pizza dough.

          I had that dream too! 😁

          this is a picture of a slice of pizza cut from a whole pie

          What is the difference between gluten free flours?

          There are so many differences between brands of flours and that was my mistake.  Bob’s Red Mill flours have fava bean flour and chickpea flour in them, which gave me dense pizzas, with not a lot of flavor and because of the “beige” color of the flour, it didn’t make the prettiest pizza.

          Rice Flour Was the Winner!

          Yep, rice flour is all white, and when paired with tapioca flour, this tastes so close to skinny pizza dough!

          Is it the same WW points as Skinny Pizza Dough?

          Yes and no.  One ounce of my skinny pizza dough is 41 calories, .1 fat, 8.3 carbs and 1.8 protein.

          One ounce of skinny gluten free dough is 51 calories, .8 fat, 9 carbs and 1.3 protein.

          Let’s say I make a pizza that is 5 ounces of skinny pizza dough – that would be 205 calories for the dough.  5 ounces of skinny gluten free pizza is 255 calories.  So for 50 more calories a pizza, I may count it as one more point, but that’s your business if you want to do that.

          If it were me, I would still count this as 1 point an ounce.  But again, you have the nutritional info you can add as a food in your WW app, and count it however you want.

          All I know is that this is delicious!  I found both the Divided Sunset Gluten Free Rice Flour and the Bob’s Red Mill Tapioca Flour at Walmart.  

          this is a photo of a package of gluten free flour

          this is a picture of a package of tapioca flour

          Note that the calories below were for generic flours – I calculated the exact calories with the two named flours that I used.

          Skinny Gluten Free Pizza

          Prep Time 5 mins

          Cook Time 12 hrs

          Servings 22 1 ounce servings

          Calories 56 kcal

          • 1.5 cups rice flour
          • .5 cups tapioca flour
          • 1 tbsp white cornmeal
          • 1 tsp yeast
          • 1 tsp salt
          • 1/2 cup nonfat Greek yogurt
          • 1/2 cup water
          • 4 tsp light butter (1 tsp for each individual pizza)
          • Mix the flours, cornmeal, yeast, and salt together.

          • Add the yogurt and water and mix until combined.

          • Store in a container with the lid slightly ajar, or a bowl with loose plastic wrap and let rise for 12 hours.

          • For each individual pizza, spread one teaspoon of light butter before you add your pizza sauce. The added fat gets you that crispy crust.

          • Use however many ounces of dough you want to make your creations!

          Notes:  Don’t skip the butter on the pizza before going in the oven – I think that’s what helped with the crispy crust.

          Calories: 56kcalCarbohydrates: 11gProtein: 1gFat: 1gSaturated Fat: 1gCholesterol: 1mgSodium: 108mgPotassium: 19mgFiber: 1gSugar: 1gVitamin A: 15IUCalcium: 1mgIron: 1mg

          .

                             this is a picture of butter spread over pizza doughthis is a picture of a pizza topped with cheese and spinach ready for the oven. this is a picture of pizza straight from the oven

           

           

           

          There are lots and tips and tricks on the original skinny pizza dough blog post – you can check that out here.

          Guys – this dough tastes just as good as my skinny pizza dough.  I AM SO HAPPY to share this with my friends/followers who can’t have gluten.  I hope you try this skinny gluten free pizza dough and let me know what you think!





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          Homemade Protein Bars (Low Carb) Recipe

          By electricdiet / September 18, 2020


          Making your own protein bars is super easy! Homemade protein bars save you money and taste so much better than the bars you can buy! 

          Six homemade protein bars on a white plate

          These keto protein bars only contain 6 healthy ingredients and use one bowl to prepare.

          You can use whatever nut or seed butter you currently prefer and they will always come out perfectly. 

          How to make homemade protein bars

          Step 1: Measure all the ingredients. Line a small loaf pan with parchment paper and set aside (or use a non-stick loaf pan).

          Step 2: In a large glass or microwave-safe bowl, combine your nut butter and sugar-free syrup. Heat it for 1 – 2 minutes in the microwave, mixing every 15 seconds until smooth and easy to mix together. 

          Step 3: Add in the coconut flour, protein powder, and stevia powder and mix well.

          Tip: How well the dough comes together depends on the brand of nut butter you use. You can add more coconut flour 1 tablespoon at a time if the dough seems to wet. Add a teaspoon or two of syrup more if the dough is too thick and not coming together easily. 

          Step 4: Add the protein bar batter to the loaf pan and press to fill the pan. Sprinkle chopped peanuts on top and press in slightly

          Step 5: Refrigerate for an hour or two until the protein bars are firm enough to be cut and served. 

          Playing with flavors

          Any nut or seed butter can be substituted in equal quantities for this recipe. Just make sure to use nut or seed butters that are natural and without any added salts and sugars to keep these homemade protein bars low-carb and diabetes-friendly. 

          Another way you can adjust the flavor of the protein bars to your liking is by switching up which protein powders you use. Vanilla, chocolate, cookies and cream, and peanut butter flavors all are really delicious and work well in these bars. 

          Storing the bars

          The protein bars can be stored for several days in the refrigerator.

          Because they are made of peanut butter, they can melt if left outside the fridge on a hot day. I recommend eating them almost straight from the fridge or keeping them cool if you want to bring them with you.

          Other low-carb snacks

          Here are a few other low-carb snack recipes you might enjoy:

          You can also read this roundup I created of 10 easy low-carb dessert recipes for even more inspiration!

          When you’ve made your own homemade protein bars, please don’t forget to let me know how you liked them and rate the recipe in the comments below!

          Recipe Card

          Easy Homemade Protein Bars

          Making your own protein bars is super easy! Homemade protein bars save you money and taste so much better than the bars you can buy! 

          Prep Time:10 minutes

          Cook Time:0 minutes

          Cooling time:1 hour

          Total Time:1 hour 10 minutes

          Servings:8

          Stack of protein bars with peanuts

          Instructions

          • Line a small loaf pan with parchment paper and set aside.

          • In a large glass or microwave-safe bowl, combine your nut butter with your sugar-free syrup. Heat it for 1 – 2 minutes in the microwave, mixing every 15 seconds until smooth and easy to mix together. 

          • Add in the coconut flour, protein powder, and stevia powder and mix well.

          • Tip: How well the dough comes together depends on the brand of nut butter you use. You can add more coconut flour 1 tablespoon at a time if the dough seems to wet. Add a teaspoon or two of syrup more if the dough is too thick and not coming together easily. 

          • Add the protein bar batter to the loaf pan and press to fill the pan. Sprinkle chopped peanuts on top and press in slightly

          • Refrigerate for an hour or two until the protein bars are firm enough to be cut and served. 

          Recipe Notes

          This recipe makes 8 servings. 
          Any nut or seed butter can be substituted in equal quantities for this recipe.
          The protein bars can be stored in the refrigerator for several days. 

          Nutrition Info Per Serving

          Nutrition Facts

          Easy Homemade Protein Bars

          Amount Per Serving

          Calories 260
          Calories from Fat 173

          % Daily Value*

          Fat 19.2g30%

          Saturated Fat 3.3g17%

          Trans Fat 0g

          Polyunsaturated Fat 0.7g

          Monounsaturated Fat 1.1g

          Cholesterol 1.4mg0%

          Sodium 66.4mg3%

          Potassium 317.2mg9%

          Carbohydrates 9.7g3%

          Fiber 6.3g25%

          Sugar 2.7g3%

          Protein 13.7g27%

          Net carbs 3.4g

          * Percent Daily Values are based on a 2000 calorie diet.

          Course: Snack

          Cuisine: American

          Keyword: Homemade Protein Bars



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