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Insulin Resistance Type 1 Diabetes

Current Place Of Metformin In Type 1 Diabetes

Lesson 1: Diabetes, Insulin, and Insulin Resistance (English)

Metformin is not approved for use in T1D by the US FDA. However, in the data from the T1D Exchange registry from the US, 6% of patients were identified as metformin users . In another Scottish registry of 1850 type 1 diabetics, 7.9% with BMI > 27 kg/m2 and 13% with BMI > 30 kg/m2 were receiving metformin . In its Standards of Care, the ADA notes that adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes . In 2015, the UK NICE guidelines recommended use of metformin in adults with type 1 diabetes with BMI 25 or BMI 23 kg/m2 for people of South Asian and related ethnic groups, who want to improve glucose control while minimizing their effective insulin dose .

Living With Insulin Resistance

Living with insulin resistance requires lifestyle changes as well as regular use of prescription medicine. You will have to be more careful in making meal and snack choices, reading labels, and maintaining a lower weight. You also will have to commit to regular exercise and take your medicines as prescribed.

How Is Insulin Resistance Diagnosed

Insulin resistance is difficult to diagnose because there isnt routine testing for it, and as long as your pancreas is producing enough insulin to overcome the resistance, you wont have any symptoms.

As theres no single test that can directly diagnose insulin resistance, your healthcare provider will consider several factors when assessing insulin resistance, including your:

  • Medical history.

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What Does It Mean To Be Insulin Resistant

Insulin resistance is clinically defined as a reduced response of target tissues to stimulation by insulin. The phenomenon of IR is accompanied by a pathological insulin secretion after a meal, which is called hyperinsulinemia. Interestingly, long-lasting hyperinsulinemia leads to aggravated IR. In line with that notion, a chronically elevated insulin level produces an adaptive reduction in the number of plasma membrane receptors for the hormone . Consequently, greater insulin dosage is required to elicit the same physiological effect, hence IR begins. Moreover, secondary alterations in target tissues are also possible. Marban et al. demonstrated that transgenic mice over-expressing insulin showed diminished insulin responsiveness despite fasting normoglycaemia and proper body weight . This could be explained by an impaired binding of insulin to its receptors and/or stem from hypertriglyceridemia, which may impair insulin signal transduction . Hyperinsulinemia may also promote weight gain, since insulin overdose results in severe hypoglycaemia and polyphagia . This leads to the formation of a specific vicious circle, i.e., hyperinsulinemia propels IR and weight gain, which, in turn, require higher insulin dosage for compensation. Moreover, also defects in the insulin receptor structure, a reduction in the density of the receptors at the cell surface, or improper action of the immune system, may lead to an abnormal response of target tissues to insulin.

Rising Prevalence Of Overweight And Obesity In Type 1 Diabetes

Diabetes mellitus type 2 Insulin resistance Type 1 diabetes, others ...

While the traditional view remains that type 1 diabetics are lean with normal body weight, the prevalence of overweight and obesity in type 1 diabetic individuals is increasing in parallel with the global population trends in weight gain . Libman et al. reported that the prevalence of overweight and obesity at onset of insulin-dependent diabetes among children almost tripled from 12.6% to 36.8% between the time periods of 19791989 and 1990-1998, following the general population trend . In several cohorts, the prevalence of overweight and obesity in T1D children was reported to be higher than in the normal population, with an estimated 22.1% of T1D children being overweight or obese in the US SEARCH for Diabetes in Youth study cohort . The median BMI was greater than the national reference values in the T1D Exchange and Diabetes Prospective Follow-up registries , particularly in the US population .

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Is It Only A Type 2 Problem

When I was first diagnosed with type 1, my approach to the whole disease was simple: In order to be as healthy as the next person, I needed to work twice as hard. I became hyper-focused on my diet and on staying active. If a normal person could stay healthy eating well 90% of the time, then I needed to eat well 99% of the time. If the normal person needed to exercise 30 minutes a day, then I needed 60.

I spent a lot of time researching superfoods, cardio health, and blood sugar stabilizing supplements. Naturally, a lot of this research led me to read about the health struggles of type 2 diabetics. Which made sense, their disease is influenced heavily by food and exercise, while ours, were told, is dictated wholly by genetics and random chance.

But the more I read, the more I started to focus on this phenomenon of insulin resistance. And the more I realized this was not an issue relegated to type 2s alone. It affects everyone, even healthy people. And if thats true, then it only stands to reason that this phenomenon can play a huge part in how well a type 1 diabetic can control their blood sugars.

Insulin Resistance Type 1 And Type 2 Diabetes And Related Complications 2017

Joseph Fomusi NdisangAccepted

In the past two decades, significant strides have been made in elucidating important mechanisms associated with insulin resistance, overt diabetes, and related cardiometabolic diseases. However, more intense research is still needed for a more comprehensive understanding of the pathophysiological profile of insulin resistance in diabetes, especially in situations where diabetes is comorbid with other chronic diseases. Therefore, this special issue is a collection of research and review papers that address a broad range of mechanisms associated with insulin resistance, type 1 diabetes, type 2 diabetes, and related cardiometabolic complications. A common pathophysiological destructive force in type 1 and type 2 diabetes is the high levels of advanced glycation end products generated by hyperglycaemia . To unveil further insights on advanced glycation end products, T. Okura et al. wrote an article on the putative pathophysiological role of advanced glycation end products on deregulation of insulin signalling in type2 diabetes. To further expatiate on dysfunctional insulin signalling, F. De C. Cartolano et al. investigated the impact of insulin resistance on lipid metabolism at preclinical level and found that insulin resistance and diabetes are powerful predictors of quantitative and qualitative features of lipoprotein dysfunction and are directly associated with increased atherogenic risk.

Joseph Fomusi Ndisang

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Does Metformin Have A Cardioprotective Effect In Type 1 Diabetes

Metformin has an established cardioprotective effect in type 2 diabetes and a similar role in T1D has been the subject of recent research. Use of metformin in T1D is associated with a reduction in several cardiovascular risk factors, including BMI, waist circumference, HbA1c, LDL cholesterol and total cholesterol. In a pilot study including 33 obese type 1 diabetic individuals, Burchardt et al. demonstrated that the addition of metformin resulted in a significant reduction in HbA1c, triglycerides, glycated LDL and BMI . In 100 type 1 diabetics randomized to metformin and placebo, Lund et al. demonstrated a significant reduction in total and LDL cholesterol with metformin, which remained significant even after adjustment for background statin use . In addition, metformin improved endothelial function in type 1 diabetic individuals . Use of metformin was associated with increased circulating endothelial progenitor cells, pro-angiogenic cells and decreased circulating endothelial cells .

REMOVAL suggests that metformin may have a direct effect on atherosclerosis progression in T1D, even in middle-aged patients with long disease duration, on a background of antihypertensive and statin therapy. This effect is unlikely to be mediated by improved glycemic control. It remains to be seen if these benefits translate into improved clinical outcomes and whether a similar reduction of cIMT occurs in adolescents and young adults who do not have CV risk factors yet.

Difference Between Insulin Resistance And Diabetes

U-M Type 1 Diabetes 101 | Module 5 | How Does Insulin Work?

Insulin resistance occurs when insulin is produced by the body but not used effectively by the cells. Insulin is a hormone that allows cells throughout the body, particularly in the liver and in the muscles, to absorb glucose and use it to create energy. Insulin resistance interferes with that absorption and can lead to the development of pre-diabetes or type 2 diabetes.

How Insulin Resistance Develops

Insulin resistance has a strong genetic factor. Native Americans, African Americans, Hispanic Americans, Asian Americans and Pacific Islanders are all at increased risk for developing insulin resistance. Ultimately, this is likely to lead to type 2 diabetes for these populations. A family history of type 2 diabetes is also an indicator of a higher risk of developing insulin resistance.

Certain medications can contribute to insulin resistance, including a number of drugs used to treat bipolar disorder as well as certain steroids.

Metabolic syndrome, a group of disorders including excess weight , high blood pressure, and elevated blood lipid levels can also cause insulin resistance.

Pregnancy, stress, infection, untreated sleep apnea or severe illnesses are other risk factors for developing insulin resistance.

How Insulin Resistance and Diabetes Differ

Diabetes results when the body stops producing insulin or when the pancreas begins to slow production of insulin after a period of high demand, often caused by insulin resistance.

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Insulin Resistance And Insulin Dose

Insulin resistance was calculated using the eGDR according to the following equation: 24.31 , where the units are mg · kg1 · min1, the WH = waist-to-hip ratio, and HT = hypertension . This formula has been adapted for the use of A1C rather than HbA1 . Insulin dose was measured in units per kilogram body weight at baseline.

What Questions Should I Ask My Doctor

If youve been diagnosed with insulin resistance, it may be helpful to ask your healthcare provider the following questions:

  • Whats causing my insulin resistance?
  • What can I do to increase my insulin sensitivity?
  • Whats my risk of developing prediabetes or Type 2 diabetes?
  • Is there any medication I can take?
  • Should I see a specialist for insulin resistance?

A note from Cleveland Clinic

Insulin resistance is a complex condition that can affect your health in several ways. Since it doesnt have any symptoms until it turns into prediabetes or Type 2 diabetes, the best thing you can do is try to prevent and reverse insulin resistance by maintaining a healthy weight, exercising regularly and eating a healthy diet. Unfortunately, though, not all causes of insulin resistance can be prevented or treated. If you have any questions about your risk of developing insulin resistance or conditions associated with it, talk you your healthcare provider. Theyre there to help you.

Last reviewed by a Cleveland Clinic medical professional on 12/16/2021.


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Causes Of Insulin Resistance

Insulin resistance is more likely if you have too much fat stored in and around your liver and pancreas. It is linked to living with overweight or obesity, but insulin resistance can affect some people of a healthy weight or BMI.

The exact cause of insulin resistance isnt fully understood and may be different from person to person.

How your body makes or uses or responds to insulin can change over time. It can be affected by everything from hormones during pregnancy or puberty to the type and amount of exercise you do.

Some people with insulin resistance live with overweight or obesity, but not everyone.

How To Reduce Insulin Resistance

[Full text] Metformin Decreases Insulin Resistance in Type 1 Diabetes ...

Not all insulin resistance is a normal, natural thing. Eating sugar-laden and overly processed foods tax the hormone systems in your body. Carrying around excess weight, especially fat deposits, ramp up the development of insulin resistance.

Type 1s are not immune to this problem, either. In fact, there is a growing number of people stricken with double diabetes type 1s who develop bad enough insulin resistance to also be considered type 2 diabetics.

A few years ago, I joined a gym for the first time since my diagnosis. Normally, I kept myself in shape by running, hiking and doing other cardio-based exercises. Now that I had access to weight machines, I started a dedicated muscle building routine. For the first time in a long time, the idea of insulin resistance was at the front of my mind. Even though my weight stayed about the same, after a couple of months with the new workout routine, my insulin needs dropped dramatically.

Even though I was thin and otherwise very healthy, that little bit of extra fat I was carrying around had caused some degree of insulin resistance that disappeared once the fat did.

I noticed a similar thing happen when I refocused my attention to eating a healthy, whole-food, plant-based diet. My insulin needs dropped and my blood sugars became a hundred times easier to manage. Without really trying, my A1C dropped below 5.5 for the first time in the eight years since my diagnosis.

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Symptoms Of Insulin Resistance

You can’t tell that you have insulin resistance by how you feel. You’ll need to get a blood test that checks your blood sugar levels.

Likewise, you wonât know if you have most of the other conditions that are part of insulin resistance syndrome without seeing your doctor.

Some signs of insulin resistance include:

  • A waistline over 40 inches in men and 35 inches in women

Increased Cardiovascular Risk: Relation With Insulin Resistance

There is a significantly high risk of cardiovascular disease in T1D, which is often attributed to hyperglycemia. Cardiovascular disease is the leading cause of death, with the life expectancy of adults aged 20 years with T1D reduced by 13 years . Vascular dysfunction and increased carotid intima media thickness are evident as early as childhood and adolescence, within a few years since onset of diabetes . The process is accelerated by insulin resistance, weight gain and obesity.

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When Should I See My Healthcare Provider About Insulin Resistance

If youve been diagnosed with insulin resistance or conditions related to insulin resistance, its important to see your healthcare provider regularly to make sure your blood sugar levels are in a healthy range and that your treatment is working.

If youre experiencing symptoms of high blood sugar or prediabetes, contact your healthcare provider. They can run simple tests to check your blood sugar levels.

If you have a family history of diabetes or conditions that can cause insulin resistance, talk to your healthcare provider about your risk of developing insulin resistance.

How Insulin Resistance Works

U-M Type 1 Diabetes 101 | Module 5 | Giving Insulin at a Meal

Insulin acts like a key that unlocks cells so they can take in glucose from the blood. Someone with insulin resistance needs more insulin to keep blood glucose from rising higher than usual.

There are a number of reasons why someone with type 1 diabetes might have insulin resistance. Risk factors include excess body weight, medications , smoking, puberty, pregnancy in the second and third trimesters, and a family history of type 2 diabetes.

If you think you have insulin resistance, talk to your health care provider. They can check the total amount of insulin youre using per day compared to your body weight. If you need to use a lot of insulin compared to your body weight, it could mean you have insulin resistance.

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Progression Of Double Diabetes

Similar to type 2 diabetes, double diabetes, if not treated appropriately can become more severe over time.

If double diabetes is allowed to progress more insulin will need to be injected which promotes further weight gain and increases the bodys resistance to the insulin further requiring even greater insulin

Insulin Resistance In Type 1 Diabetes

There are obvious technical difficulties in estimating insulin sensitivity in individuals with T1D using traditional methods, and the hyperinsulinemic euglycemic clamp remains the gold standard . Insulin resistance is often observed in type 1 diabetics during pubertal development and inter-current illness. Puberty is associated with a physiological impairment of insulin sensitivity, related to the surge in growth hormone and sex steroids, especially during the later stages of pubertal development. Puberty-related insulin resistance mainly affects peripheral glucose utilization, with less effect on fat metabolism . However, insulin resistance may be more common in T1D and was demonstrated as early as 1982 by DeFronzo et al. . Poor glycemic control in type 1 diabetics is associated with hepatic insulin resistance, while whole-body glucose utilization was reported to be lower even in those who were well controlled .

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Insulin Resistance Treatment And Prevention

You can take steps to reverse insulin resistance and prevent type 2 diabetes:

  • Exercise. Go for at least 30 minutes a day of moderate activity 5 or more days a week. If you’re not active now, work up to that.
  • Get to a healthy weight. If you’re not sure what you should weigh or how to reach a weight loss goal, ask your doctor. You may also want to talk with a nutritionist and a certified personal trainer.
  • Eat a healthy diet. Think fruits, vegetables, whole grains, nuts, beans, fish, legumes, and other lean protein.
  • Take medications. Your doctor may prescribe a medication called metformin to help keep your blood sugar in check.

Insulin Blood Sugar And Type 2 Diabetes

Figure 1 from Resistin Visfatin Leptin Atherosclerosis Obesity ...

Insulin is a key player in developing type 2 diabetes. This vital hormoneyou cant survive without itregulates blood sugar in the body, a very complicated process. Here are the high points:

  • The food you eat is broken down into blood sugar.
  • Blood sugar enters your bloodstream, which signals the pancreas to release insulin.
  • Insulin helps blood sugar enter the bodys cells so it can be used for energy.
  • Insulin also signals the liver to store blood sugar for later use.
  • Blood sugar enters cells, and levels in the bloodstream decrease, signaling insulin to decrease too.
  • Lower insulin levels alert the liver to release stored blood sugar so energy is always available, even if you havent eaten for a while.

Thats when everything works smoothly. But this finely tuned system can quickly get out of whack, as follows:

  • A lot of blood sugar enters the bloodstream.
  • The pancreas pumps out more insulin to get blood sugar into cells.
  • Over time, cells stop responding to all that insulintheyve become insulin resistant.
  • The pancreas keeps making more insulin to try to make cells respond.
  • Eventually, the pancreas cant keep up, and blood sugar keeps rising.

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