Type 2 Diabetes / insulin resistance / pre-diabetes

Type 2 diabetes is an impairment in the way the body regulates and uses sugar (glucose) as a fuel. This long-term (chronic) condition results in too much sugar circulating in the bloodstream. Eventually, high blood sugar levels can lead to disorders of the circulatory, nervous and immune systems. Type 2 diabetes used to be known as adult-onset diabetes, but both type 1 and type 2 diabetes can begin during childhood and adulthood. Type 2 is more common in older adults, but the increase in the number of children with obesity has led to more cases of type 2 diabetes in younger people.

Epidemiology

According to WHO, he number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. Prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. Between 2000 and 2019, there was a 3% increase in diabetes mortality rates by age. In 2019, diabetes and kidney disease due to diabetes caused an estimated 2 million deaths.

Pathophysiology and causes of type 2 Diabetes

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease.

Q10

A-lipoic acid

PQQ

Q10

Forty studies (n = 2,424 participants) were included in this meta-analysis. CoQ10 significantly reduced fasting glucose (WMD: -5.22 [95% CI: -8.33, -2.11] mg/dl; P <0.001; I2=95.10%), fasting insulin (-1.32 [-2.06, -0.58] μIU/ml; P < 0.001; I2=78.86%), HbA1c (-0.12% [-0.23, -0.01]; P =0.04; I2=49.10%), and HOMA-IR (-0.69 [-1.00, -0.38]; P <0.001; I2=88.80%). The effect of CoQ10 on outcomes was greater in diabetes with lower heterogeneity. A “U” shape dose-response relationship curve revealed that 100-200 mg/day of CoQ10 largely decreased fasting glucose (χ2 = 12.08, Pnonlinearity =0.002), fasting insulin (χ2 = 9.73, Pnonlinearity =0.008), HbA1c (χ2 = 6.00, Pnonlinearity =0.049), HOMA-IR (χ2 = 25.89, Pnonlinearity <0.001).

Interpretation: CoQ10 supplementation has beneficial effects on glycemic control, especially in diabetes, and 100-200 mg/day of CoQ10 could achieve the greatest benefit, which could provide a basis for the dietary guidelines of CoQ10 in patients with glycemic disorders.

J Clin Endocrinol Metab . Eclinical medicine, VOLUME 52, 101602, OCTOBER 01, 2022, DOI:https://doi.org/10.1016/j.eclinm.2022.101602

A-lipoic acid

The role of ALA as an insulin-sensitizing agent for cells has been recognized since the mid-1990s. In 1995, a trial of 13 patients with type 2 diabetes given a single infusion of ALA (1,000 mg) showed a 50% reduction in insulin-stimulated glucose disposal versus those given a placebo.45 Since then, many studies have corroborated the role of ALA as an insulin-sensitizing agent. A meta-analysis of 24 studies published in 2018 concluded that ALA improved glucose homeostasis as well as lipid profiles in subjects with metabolic syndrome.

Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69.

These diverse actions suggest that lipoic acid acts by multiple mechanisms, many of which have only been uncovered recently. In this review we briefly summarize the known biochemical properties of lipoic acid and then discussed the oxidative mechanisms implicated in diabetic complications and the mechanisms by which lipoic acid may ameliorate these reactions. The findings of some of the clinical trials in which lipoic acid administration has been tested in diabetic patients during the last 10 years are summarized. It appears that the clearest benefit of lipoic acid supplementation is in patients with diabetic neuropathy.

Front Pharmacol. 2011; 2: 69. Published online 2011 Nov 17. doi: 10.3389/fphar.2011.00069