Insulin dose-response studies in severely insulin-resistant type 2 diabetes--evidence for effectiveness of very high insulin doses.

AIM: To combat diabetic complications strict glycaemic control is desirable in type 2 diabetes, but some patients are severely insulin resistant and it is not known whether high doses of insulin are effective. This study was designed to determine the acute dose-response effects of insulin in patients with type 2 diabetes and severe insulin resistance. METHODS: We included eight insulin-resistant (mean insulin dose: 186 IU/day; body mass index: 35) subjects with type 2 diabetes in a single-blinded, randomized crossover study. Each subject was studied on two occasions. On each occasion, subjects underwent two 3-h hyperinsulinaemic euglycaemic clamps. The subjects were randomized to two low-dose insulin infusions (0.5 and 1.5 mU/kg/min in random order) on one occasion and to two high-dose insulin infusions (3.0 and 5.0 mU/kg/min in random order) on another occasion. RESULTS: On all occasions, steady-state glucose infusion rates (SSGIRs) were accomplished and we observed a clear dose-response relationship with GIR values of 0.4 ± 0.2 (s.e.), 2.6 ± 0.6, 3.7 ± 0.8 and 4.9 ± 0.9 mg/kg/min during the 0.5, 1.5, 3.0 and 5.0 mU/kg/min insulin infusions, respectively (p < 0.001). Likewise, there was a dose-dependent suppression of endogenous glucose production (EGP) (p < 0.009), plasma free fatty acids (FFAs) (p < 0.001) and plasma glucagon (p = 0.001). CONCLUSIONS: Our results show that the insulin dose response in terms of GIR and EGP is preserved for insulin doses corresponding to >800 IU/day, suggesting effectiveness of very high insulin doses in severely insulin-resistant subjects.

Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels - results from a randomized trial.

BACKGROUND: Low plasma 25-hydroxy-vitamin D (25OHD) is associated with obesity. Vitamin D (VD) may be implicated in obesity and its complications such as insulin resistance, hypertension, and low-grade inflammation. We investigated the effects of VD supplementation on fat distribution and on obesity complications in obese adults with low plasma levels of 25OHD. METHODS: In a double-blind design 52 subjects aged 18 to 50years with BMI>30kg/m(2) and plasma 25OHD <50nmol/l were randomized to 26weeks of treatment with 7000IU of VD daily or placebo. Body composition was assessed by DXA and subcutaneous (SAT) and visceral adipose tissue (VAT), intrahepatic (IHL) and intramyocellular lipids (IMCL) were evaluated by magnetic resonance imaging and magnetic resonance spectroscopy. Insulin resistance (HOMA-IR), blood pressure, plasma lipids, and circulating inflammatory markers were also investigated. RESULTS: VD treatment increased mean plasma levels of 25OHD from 33nmol/l to 110nmol/l (P<0.0001) and decreased median parathyroid hormone levels from 5.3 to 4.5pmol/l (P<0.01) in the intervention group. Treatment did not change body fat, SAT, VAT, IHL, or IMCL compared with placebo. Neither did treatment affect HOMA, blood pressure, plasma lipids or any of several inflammatory markers investigated including hsCRP. CONCLUSION: Increasing 25OHD levels by VD treatment for 26weeks have no effects on obesity complications in obese adults with low baseline plasma 25OHD.