Pregnant type 1 diabetes women with rises in C-peptide display higher levels of regulatory T cells: A pilot study.

AIM: During pregnancy of type 1 diabetes (T1D) women, a C peptide rise has been described, which mechanism is unclear. In T1D, a defect of regulatory T cells (Tregs) and its major controlling cytokine, interleukin-2 (IL2), is observed. METHODS: Evolution of clinical, immunological (Treg (CD4+CD25hiCD127-/loFoxp3+ measured by flow cytometry and IL2 measured by luminex xMAP technology) and diabetes parameters (insulin dose per day, HbA1C, glycaemia, C peptide) was evaluated in 13 T1D women during the three trimesters of pregnancy and post-partum (PP, within 6 months) in a monocentric pilot study. Immunological parameters were compared with those of a healthy pregnant cohort (QuTe). RESULTS: An improvement of beta cell function (C peptide rise and/or a decrease of insulin dose-adjusted A1c index that estimate individual exogenous insulin need) was observed in seven women (group 1) whereas the six others (group 2) did not display any positive response to pregnancy. A higher level of Tregs and IL2 was observed in group 1 compared to group 2 during pregnancy and at PP for Tregs level. However, compared to the healthy cohort, T1D women displayed a Treg deficiency CONCLUSION: This pilot study highlights that higher level of Tregs and IL2 seem to allow improvement of endogenous insulin secretion of T1D women during pregnancy.

Five-year mortality in patients with diabetic foot ulcer during 2009-2010 was lower than expected.

AIM: Mortality rates are decreasing in patients with diabetes. However, as this observation also concerns patients with diabetic foot ulcer (DFU), additional data are needed. For this reason, our study evaluated the 5-year mortality rate in patients with DFU during 2009-2010 and identified risk factors associated with mortality. METHODS: Consecutive patients who attended a clinic for new DFU during 2009-2010 were followed until healing and at 1 year. Data on mortality were collected at year 5. Multivariate Cox proportional-hazards model was used to identify mortality risk factors. RESULTS: A total of 347 patients were included: mean age was 65±12 years, diabetes duration was 16 [10; 27] years; 13% were on dialysis; and 7% had an organ transplant. At 5 years, 49 patients (14%) were considered lost to follow-up. Total mortality rate at 5 years was 35%, and 16% in patients with neuropathy. On multivariate analyses, mortality was positively associated with: age [hazard ratio (HR): 1.05 (1.03-1.07), P<0.0001]; duration of diabetes [HR: 1.02 (1.001-1.03], P=0.03]; PEDIS perfusion grade 2 vs. 1 [HR: 2.35 (1.28-4.29), P=0.006)]; PEDIS perfusion grade 3 vs. 1 [HR: 3.14 (1.58-6.24), P=0.001); and ulcer duration at year 1 [HR 2.09 (1.35-3.22), P=0.0009]. CONCLUSION: Mortality rates were not as high as expected despite the large number of comorbidities, suggesting that progress has been made in the health management of these patients. In particular, patients with neuropathic foot ulcer had a survival rate of 84% at 5 years.

What is the evidence for metabolic surgery for type 2 diabetes? A critical perspective.

Bariatric surgery has emerged as a highly effective treatment not only for obesity, but also for type 2 diabetes (T2D). A meta-analysis has reported the complete resolution of T2D in 78.1% of cases of morbidly obese patients after bariatric surgery. Such extraordinary results obtained in diabetic patients with body mass index (BMI) scores>35kg/m2 have led investigators to question whether similar results might be achieved in patients with BMIs<35kg/m2. Preliminary studies suggest that metabolic surgery is safe and effective in patients with T2D and a BMI<35kg/m2, whereas other studies report that metabolic surgery is less effective for promoting T2D remission in these patients. Thus, the results are discordant. Long-term studies would be useful for determining the safety, efficacy and cost-effectiveness of metabolic surgery for this population with T2D. In 2015, it is probably premature to say that metabolic surgery is an accepted treatment option for T2D patients with BMIs<35kg/m2.

What can bariatric surgery teach us about the pathophysiology of type 2 diabetes?

Bariatric surgery is indicated in cases of severe obesity. However, malabsorption-based techniques (gastric bypass and biliopancreatic diversion, both of which exclude the duodenum and jejunum from the alimentary circuit), but not restrictive techniques, can abolish type 2 diabetes within days of surgery, even before any significant weight loss has occurred. This means that calorie restriction alone cannot entirely account for this effect. In Goto-Kakizaki rats, a type 2 diabetes model, glycaemic equilibrium is improved by surgical exclusion of the proximal intestine, but deteriorates again when the proximal intestine is reconnected to the circuit in the same animals. This effect is independent of weight, suggesting that the intestine is itself involved in the immediate regulation of carbohydrate homoeostasis. In humans, the rapid improvement in carbohydrate homoeostasis observed after bypass surgery is secondary to an increase in insulin sensitivity rather than an increase in insulin secretion, which occurs later. Several mechanisms are involved--disappearance of hypertriglyceridaemia and decrease in levels of circulating fatty acids, disappearance of the mechanisms of lipotoxicity in the liver and skeletal muscle, and increases in secretion of GLP-1 and PYY--and may be intricately linked. In the medium term and in parallel with weight loss, a decrease in fatty tissue inflammation (which is also seen with restrictive techniques) may also be involved in metabolic improvement. Other mechanisms specific to malabsorption-based techniques (due to the required exclusion of part of the intestine), such as changes in the activity of digestive vagal afferents, changes in intestinal flora and stimulation of intestinal neoglucogenesis, also need to be studied in greater detail. The intestine is, thus, a key organ in the regulation of glycaemic equilibrium and may even be involved in the pathophysiology of type 2 diabetes.