Category Archives: Causes of Diabetes

The Hygiene Hypothesis and Type 1 Diabetes Mellitus

An agroforestry area

D.P. Strachan in 1958 proposed an idea called the “hygiene hypothesis.” The theory is that infections and exposure to microbes (germs) in early life decreases the incidence of allergic and autoimmune diseases such as type 1 diabetes, asthma, and atopic dermatitis. Autoimmune and allergic diseases seem to be on the rise for more than a half-century, perhaps related to our urbanized lifestyles that have taken us away from the germ-rich environment of farms and forests. And we do our best to sterilize our homes with antimicrobial soaps, countertop cleaners, and hand sanitizers that we didn’t use even 20 years ago.

Exactly how early-life exposure to infections and germs could lead to autoimmune and allergic diseases is beyond the scope of today’s post. I’ll just say that germ exposure may help teach our immune system to better regulate itself. In case you don’t know, the immune system plays a large role in allergic diseases and symptoms.

A recent study out of Finland supports the hygiene hypothesis and was published in Diabetes Care:

OBJECTIVE Environmental microbial exposures have been implicated to protect against immune-mediated diseases such as type 1 diabetes. Our objective was to study the association of land cover around the early-life dwelling with the development of islet autoimmunity and type 1 diabetes to evaluate the role of environmental microbial biodiversity in the pathogenesis.

RESEARCH DESIGN AND METHODS Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease-associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies.

RESULTS Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16–0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity.

CONCLUSIONS The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry areas) early in life is inversely associated with the risk of type 1 diabetes. This association may be mediated by early exposure to environmental microbial diversity.


From the introduction:

“The incidence of type 1 diabetes has increased during the past 70 years in the developed countries paralleling similar increase in other immune-mediated diseases such as allergies and asthma. The rapid increase, together with the conspicuous variation in incidence rates between countries, supports the role of environmental factors in the pathogenesis. Overall, the incidence rate tends to be high in countries located in the north, although exceptions to this trend exist.

“Living in an agricultural environment and contacts with farm animals and pets at home has been associated with a higher microbial diversity indoors and a decreased risk of allergic diseases. Although the mechanisms of this phenomenon are not fully understood, several lines of evidence suggest that exposure to environmental microbial diversity and direct soil contacts may play a role. This, in turn, could lead to the activation of immunoregulatory pathways suppressing overreactive immune responses, as presented by the biodiversity hypothesis. A wide exposure of the skin and mucosal surfaces to all kinds of microbes, including bacteria, viruses, and eukaryotes, regardless of whether they are infecting or colonizing humans, could provide constant immunological stimulation to the immune system, which is needed for the development of healthy immune regulation.

“As with allergic diseases, type 1 diabetes is also associated with failure to control hyperreactive immune responses. In type 1 diabetes, these immune responses target β-cell autoantigens instead of allergens.” 


Steve Parker, M.D.

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Overweight Men Reduce Insulin Resistance Via Resistance Exercise Training

Didn’t we already know this?

Insulin is a blood-borne hormone that the pancreas gland secretes in order to keep blood sugar levels from getting too high. (Insulin does many other things, but table that for now.) Insulin triggers certain body cells to absorb glucose from the bloodstream. “Insulin resistance” means that these cells don’t respond to insulin as well as they should, so either the pancreas secretes even more insulin (hyperinsulinemia) or blood sugar levels rise. Insulin resistance is a harbinger of type 2 diabetes mellitus. Most overweight or obese type 2 diabetics have insulin resistance. Many experts think hyperinsulinemia causes disease by itself, regardless of blood sugar levels. So it may be best to avoid insulin resistance and hyperinsulinemia.

The aim of the study was to investigate the effects of 6 weeks of resistance exercise training, composed of one set of each exercise to voluntary failure, on insulin sensitivity and the time course of adaptations in muscle strength/mass. Ten overweight men (age 36 ± 8 years; height 175 ± 9 cm; weight 89 ± 14 kg; body mass index 29 ± 3 kg m−2) were recruited to the study. Resistance exercise training involved three sessions per week for 6 weeks. Each session involved one set of nine exercises, performed at 80% of one‐repetition maximum to volitional failure. Sessions lasted 15–20 min. Oral glucose tolerance tests were performed at baseline and post‐intervention. Vastus lateralis muscle thickness, knee‐extensor maximal isometric torque and rate of torque development (measured between 0 and 50, 0 and 100, 0 and 200, and 0 and 300 ms) were measured at baseline, each week of the intervention, and after the intervention. Resistance training resulted in a 16.3 ± 18.7% (P < 0.05) increase in insulin sensitivity (Cederholm index). Muscle thickness, maximal isometric torque and one‐repetition maximum increased with training, and at the end of the intervention were 10.3 ± 2.5, 26.9 ± 8.3, 18.3 ± 4.5% higher (P < 0.05 for both) than baseline, respectively. The rate of torque development at 50 and 100 ms, but not at 200 and 300 ms, increased (P < 0.05) over the intervention period. Six weeks of single‐set resistance exercise to failure results in improvements in insulin sensitivity and increases in muscle size and strength in young overweight men.

Source: The effect of short‐duration resistance training on insulin sensitivity and muscle adaptations in overweight men – Ismail – 2019 – Experimental Physiology – Wiley Online Library

Steve Parker, M.D.

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Proton Pump Inhibitors Linked to Type 2 Diabetes

prilosec, proton pump inhibitor
Neither the cited study nor I implicate Prilosec in particular

Regular use of proton-pump inhibitors (PPIs) increases patients’ risk of developing type 2 diabetes mellitus (T2DM) by 24%, an observational study published in Gut has suggested.

Source: Regular use of PPIs linked with increased risk of type 2 diabetes, study suggests | News | Pharmaceutical Journal

Proton pump inhibitors are widely used in the U.S. to treat esophageal reflux, ulcers, and dyspepsia. They are among the most widely prescribed drugs. You can also get them over-the-counter. Brand names include Protonix, Prilosec, and Nexium.

The study at hand defined “regular use” as at least twice per week. The study was an epidemiological one observing participants for 10-12 years. The more years of regular use, the greater risk of diabetes developing. Nearly all participants were White, so results may not apply to other ethnicities.

Note that this study doesn’t prove that PPIs cause diabetes. They just found a statistical linkage. As you know, correlation does not equal causation. We don’t know how PPIs could cause T2 diabetes. From the article:

According to the study, the possible mechanism for the association could be related to gut microbiota, as previous studies have shown that PPI use is associated with reduced diversity of gut microbiome and consistent changes in the microbiota phenotype.

Steve Parker, M.D.

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Carbohydrate-Restricted Eating Increased Risk of Type 2 Diabetes!?

Eating this reduces risk of type 2 diabetes?

This is a real head-scratcher for me, just based on the abstract. I can’t explain or write-off the researchers findings at this point. I hope they administered the food frequency questionnaire more than once. If not, I can’t take this seriously.

Highlights

•Of 9689 middle-aged Australian women, 10% developed type 2 diabetes over 15 years.

•Carbohydrate restriction was associated with a 27% higher risk of type 2 diabetes.

•This association was attenuated after adjustment for BMI.

•The association was comparable for women with and without prior gestational diabetes.

•Women should be advised to avoid carbohydrate restricted diets low in fruit and grains.

Abstract

Background and aims

Low-carbohydrate diets (LCDs) are increasingly popular but may be nutritionally inadequate. We aimed to examine if carbohydrate restriction in midlife is associated with risk of developing type 2 diabetes (T2DM), and if this association differs by previous gestational diabetes (GDM) diagnosis.

Methods and results

Dietary intake was assessed for 9689 women from the Australian Longitudinal Study on Women’s Health in 2001 (aged 50–55) and 2013 (aged 62–67) via validated food frequency questionnaires. Average long-term carbohydrate restriction was assessed using a low-carbohydrate diet score (highest quartile (Q4) indicating lowest proportion of energy from carbohydrates). Incidence of T2DM between 2001 and 2016 was self-reported at 3-yearly surveys. Log-binomial regression was used to estimate relative risks (RR) and 95% CIs. During 15 years of follow-up, 959 women (9.9%) developed T2DM. Carbohydrate restriction was associated with T2DM after adjustment for sociodemographic factors, history of GDM diagnosis and physical activity (Q4 vs Q1: RR 1.27 [95% CI 1.10, 1.48]), and this was attenuated when additionally adjusted for BMI (1.10 [0.95, 1.27]). Carbohydrate restriction was associated with lower consumption of fruit, cereals and high-fibre bread, and lower intakes of these food groups were associated with higher T2DM risk. Associations did not differ by history of GDM (P for interaction >0.15).

Conclusion

Carbohydrate restriction was associated with higher T2DM incidence in middle-aged women, regardless of GDM history. Health professionals should advise women to avoid LCDs that are low in fruit and grains, and to consume a diet in line with current dietary recommendations.

Source: Carbohydrate restriction in midlife is associated with higher risk of type 2 diabetes among Australian women: A cohort study – Nutrition, Metabolism and Cardiovascular Diseases

Steve Parker, M.D.

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After Gestational Diabetes, How Do You Prevent Type 2 Diabetes?

Baby is still a few months away

From the Journal of the Academy of Nutrition and Dietetics:

Based on the current evidence, a specific dietary intervention for diabetes prevention in women with prior GDM [gestational diabetes mellitus] can therefore not be recommended. Previous systematic reviews have also consistently concluded that evidence for an effect of combined diet and physical activity interventions is inconclusive, with the exception of strong evidence from the Diabetes Prevention Program. Findings from that intensive intervention that focused on diet and physical activity to achieve and maintain weight loss of at least 7% of initial body weight showed >50% reduction in the risk of developing T2DM in women at high risk of T2DM including women with previous GDM; however, this personalised lifestyle intervention is unlikely to be feasible for implementation in routine care. As a limited number of studies have examined diet-alone and physical activity-alone interventions, it remains unclear which diabetes prevention approach would be most effective for women with a GDM history.

Source: The Role of Diet in the Prevention of Diabetes among Women with Prior Gestational Diabetes: A Systematic Review of Intervention and Observational Studies – Journal of the Academy of Nutrition and Dietetics

If it were me? I’d lose the excess weight with a reasonable diet and exercise regularly.

Steve Parker, M.D.

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Ultra-Processed Foods May Cause Diabetes

 

One example of UPF

A recent observational study done in France found an association between incidence of type 2 diabetes and consumption of ultra-processed foods.

What are ultra-processed foods? From the study at hand, “Ultraprocessed foods (UPF) (ie, foods undergoing multiple physical, biological, and/or chemical processes, among which mostly of exclusive industrial use, and generally containing food additives) are widespread worldwide and especially in Western diets, representing between 25% and 60% of total daily energy [calories].”

These results suggest an association between UPF consumption and type 2 diabetes risk. They need to be confirmed in large prospective cohorts in other settings, and underlying mechanisms need to be explored in ad hoc epidemiological and experimental studies. Beyond nutritional factors, nonnutritional dimensions of the diet may play a role in these associations, such as some additives, neoformed contaminants, and contact materials. Even if a causal link between UPF and chronic diseases cannot be established so far, the accumulation of consistent data leads public health authorities in several countries such as France or Brazil to recommend privileging the consumption of unprocessed/minimally processed foods, and limiting the consumption of UPF in the name of the precautionary principle.

Source: Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort | Lifestyle Behaviors | JAMA Internal Medicine | JAMA Network

Steve Parker, M.D.

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LCHF Diet Improves Metabolic Syndrome Even Without Weight Loss

Use the search box to find the recipe for this LCHF avocado chicken soup

“Metabolic syndrome” may be a new term for you. It’s a collection of clinical features that are associated with increased future risk of type 2 diabetes and atherosclerotic complications such as heart attack and stroke. One in six Americans has metabolic syndrome. Diagnosis requires at least three of the following five conditions:

  • high blood pressure (130/85 or higher, or using a high blood pressure medication)
  • low HDL cholesterol:  under 40 mg/dl (1.03 mmol/l) in a man, under 50 mg/dl (1.28 mmol/l) in a women (or either sex taking a cholesterol-lowering drug)
  • triglycerides over 150 mg/dl (1.70 mmol/l) (or taking a cholesterol-lowering drug)
  • abdominal fat:  waist circumference 40 inches (102 cm) or greater in a man, 35 inches (89 cm) or greater in a woman
  • fasting blood glucose over 100 mg/dl (5.55 mmol/l)

One approach to improving the numbers is a low-carb, high-fat (LCHF) diet. Here’s a journal article abstract from JCI Insight:

BACKGROUND. Metabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.

METHODS. Individuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.

RESULTS. Despite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.

CONCLUSION. Consistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.

TRIAL REGISTRATION. ClinicalTrials.gov Identifier: NCT02918422.

FUNDING. Dairy Management Inc. and the Dutch Dairy Association.

Source: JCI Insight – Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss

Steve Parker, M.D.

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High Diabetes Rate in South Asians in the U.S. Is Not Related to Body Composition (e.g., High BMI)

Indian woman cooking chapati

“We did not identify strong evidence that accounting for body composition explains differences in the risk for type 2 diabetes. Future prospective studies of the MESA and MASALA cohorts are needed to understand how adipose tissue impacts the risk for type 2 diabetes and how to best assess this risk.”

So the high incidence of diabetes and prediabetes in South Asians in the U.S. is related to genetics or diet or activity levels?

Source: Body Composition and Diabetes Risk in South Asians: Findings From the MASALA and MESA Studies | Diabetes Care

Steve Parker, M.D.

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THIS May Be Why Americans Are Fat

Your average Americans

There’s no shortage of speculation as to why 70% of us in the U.S. are overweight or obese. A few possibilities include:

  • we’re too sedentary
  • we eat too many carbohydrates
  • we eat too much fat
  • our foods are over-processed
  • we eat away from home too often
  • we eat too many industrial seed oils
  • our water and food are contaminated with persistent organic pollutants that disrupt our endocrine systems

I was reading an article at Nutrition Today and came across this graph of calorie consumption change from 1971 to 2004 (or 2000?):

The verbal summary is from this article cited by the cited by the Nutrition Today authors: During 1971—2000, a statistically significant increase in average energy intake occurred. For men, average energy intake increased from 2,450 kcals to 2,618 kcals, and for women, from 1,542 kcals to 1,877 kcals. So men’s daily calorie intake went up by 168, and women’s by 335.

The original article I read states, alternatively, that men’s daily caloric consumption rose from 2450 to 2693, a gain of 243. I can’t explain the discrepancy between 243 and 168, nor why 2004 is in the graph instead of 2000.

Maybe you don’t think an extra 168 calories a day is much. If you believe in the validity of the Energy Balance Equation, those 168 daily calories will turn into  17.5 pounds of fat in a year unless you “burn them off” somehow. If you weigh 150 lb (68 kg), you can burn those 168 calories by doing a daily 15-minute jog at 5.5 mph (8.9 km/hr). But you ain’t gonna do that, are you?! (I’m not getting into a debate about validity of the equation now; for another perspective, read Lyle McDonald.)

But year 2000 was a long time ago. How much are Americans eating now? According to a 2016 report from Pew Research Center:

Broadly speaking, we eat a lot more than we used to: The average American consumed 2,481 calories a day in 2010, about 23% more than in 1970. That’s more than most adults need to maintain their current weight, according to the Mayo Clinic’s calorie calculator. (A 40-year-old man of average height and weight who’s moderately active, for instance, needs 2,400 calories; a 40-year-old woman with corresponding characteristics needs 1,850 calories.)

Bottom line? We’re eating more than we did in 1970. Which could explain why we’re fat. Unless we’re burning more calories than we did in 1970, which I doubt.

Steve Parker, M.D.

PS: In scientific literature, kcal is what everybody else calls a calorie.

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Skipping Breakfast May Increase Your Risk of Type 2 Diabetes

“In total 6 studies, based on 96,175 participants and 4935 cases, were included. The summary RR for type 2 diabetes comparing ever with never skipping breakfast was 1.33 (95% CI: 1.22, 1.46, n = 6 studies) without adjustment for BMI, and 1.22 (95% CI: 1.12, 1.34, n = 4 studies) after adjustment for BMI. Nonlinear dose-response meta-analysis indicated that risk of type 2 diabetes increased with every additional day of breakfast skipping, but the curve reached a plateau at 4–5 d/wk, showing an increased risk of 55% (summary RR: 1.55; 95% CI: 1.41, 1.71). No further increase in risk of type 2 diabetes was observed after 5 d of breakfast skipping/wk (P for nonlinearity = 0.08).

Conclusions

This meta-analysis provides evidence that breakfast skipping is associated with an increased risk of type 2 diabetes, and the association is partly mediated by BMI.”

Source: Breakfast Skipping Is Associated with Increased Risk of Type 2 Diabetes among Adults: A Systematic Review and Meta-Analysis of Prospective Cohort Studies | The Journal of Nutrition | Oxford Academic

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