Demographic and clinical features of critically ill patients with COVID-19 in Greece: The burden of diabetes and obesity.

AIMS: The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. METHODS: In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. RESULTS: The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. CONCLUSIONS: Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece.

Insulin effect on leucine kinetics in type 2 diabetes mellitus.

Insulin-induced glucose disposal is impaired in Type 2 diabetes mellitus (T2DM). To determine whether insulin-induced suppression of protein breakdown also is impaired, we measured leucine flux (an index of protein breakdown) in diabetic and nondiabetic subjects during a hyperinsulinemic euglycemic clamp. To avoid the confounding effects of a difference in baseline glucose, glucose concentration in the diabetic subjects was normalized by means of an overnight insulin infusion. Despite higher plasma insulin levels (33.5+/-0.05 vs 132+/-2.7 pmol/l, p<01) diabetic subjects had similar amino acid concentrations and leucine flux (96.9+/-5.8 vs 93.4+/-3.7 micromol/kg/h) as nondiabetic subjects. Infusion of insulin (0.5 mU/kg/min) increased insulin levels (p<0.01) to identical levels in both groups (218+/-16 vs 222+/-19), but the glucose infusion required to maintain euglycemia was higher (p<0.01) in nondiabetic than in diabetic subjects, indicating insulin resistance to glucose disposal in the diabetic subjects. In contrast, leucine flux (81.3+/-4.8 vs 81.6+/-3.4 micromol/kg/h) reached identical levels in both groups. The individual and total amino acid levels also were comparable in both groups. We conclude that suppression of whole body protein turnover in response to an acute increase in insulin is normal in people with T2DM. However, chronic adaptation to high insulin levels occurs, thereby enabling protein breakdown and amino acid concentration to remain within the normal range in people with T2DM.

Therapeutic effect of glibenclamide in a fixed combination with metformin or phenformin in NIDDM patients.

The combination of a sulfonylurea with a biguanide improves the pancreatic beta-cell insulin secretion and the insulin utilization in peripheral tissues in NIDDM. This open, crossover, randomised and prospective study was designed to compare the effects of the fixed combination glibenclamide-metformin (GL-METF)-2.5 and 400 mg respectively, with the fixed combination glibenclamide-phenformin (GL-PHEN)-2.5 and 25 mg respectively, on NIDDM diabetes control. Thirty NIDDM patients, in ideal metabolic control, who were being treated with GL-PHEN were divided in two groups. One group received GL-PHEN for 12 weeks followed by 12 weeks treatment with GL-METF and the reverse treatment was given to the second group. A statistically significant decrease of post-prandial blood glucose (p = 0.034) and glycosylated haemo-globin (p < 0.02) values was observed under GL-METF treatment compared to those with GL-PHEN. The values of lactic acid were within normal limits during both treatments. The insulin secretion after breakfast was similar with both drug compounds. The BMI of the patients remained the same during a follow-up study of 24 weeks. Lipid metabolism did not change significantly during the trial and the safety parameters (renal and liver function, full blood count) remained unchanged. In conclusion, the administration of GL-METF leads to better diabetes control in NIDDM patients compared to that of GL-PHEN.

The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas.

On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics.

Effects of two new alpha-glucosidase inhibitors on glycemic control in patients with insulin-dependent diabetes mellitus.

BAYo1248 and BAYm1099 are two new alpha-glucosidase inhibitors. Postprandial glucose tolerance was significantly improved and postprandial insulin requirements were significantly reduced as compared to placebo after breakfast and lunch when 20 mg BAYo1248 were administered prior to breakfast and after breakfast, lunch and dinner when 50 mg BAYm1099 were given prior to all three main meals. Postprandial breath H2 concentrations were mildly increased when these alpha-glucosidase inhibitors were given and no patient complained of any adverse effects (such as flatulence, abdominal pain or diarrhea). BAYo1248 and BAYm1099 might be useful adjuncts to insulin in the treatment of patients with insulin-dependent diabetes mellitus.