Shigeo Imamura

The ratio of leptin to adiponectin can be used as an index of insulin resistance

The level of leptin increases with obesity, whereas that of adiponectin decreases with obesity. It is reported that the ratio of leptin to adiponectin (L/A) is associated with insulin resistance. It is difficult to evaluate insulin resistance in diabetic patients who have a dysfunction of insulin secretion. The aim of this study was to examine whether the L/A ratio is a useful marker for insulin resistance in diabetic patients. We examined L/A in the serum of a total of 139 Japanese patients with type 2 diabetes mellitus (66 women and 73 men) and 7 healthy individuals recruited in our hospital. Changes in the levels of leptin and adiponectin were observed using the oral glucose tolerance test and a hyper- and euglycemic clamp test. Twenty-one patients with type 2 diabetes mellitus were observed for more than 6 months after treatment with pioglitazone, and 31 patients with type 2 diabetes mellitus were observed for more than 6 months after the treatment with metformin. The mean value of L/A in 139 Japanese patients with type 2 diabetes mellitus was 1.22 +/- 1.41 (1.68 +/- 1.76 in women, 0.81 +/- 0.80 in men; P = .0002). In the clamp tests, L/A correlated with glucose infusion rate (GIR) (r(2) = 0.26, P = .0034). The correlation of L/A and GIR indicated a stronger correlation than either leptin (r(2) = 0.144, P = .03) or adiponectin alone (r(2) = 0.023, P = .41), or the homeostasis model assessment of insulin resistance (r(2) = 0.103, P = .08). The average hemoglobin A(1c) (HbA(1c)) improved from 10.2% +/- 1.2% to 9.2% +/- 1.6% (P = .0037) in 6 months after treatment with pioglitazone. Our results indicate pioglitazone to be effective for HbA(1c) improvement in subjects with high L/A and low L/A. The average HbA(1c) improved from 9.2% +/- 0.9% to 8.0% +/- 1.2% (P = .0002) in 6 months after treatment with metformin. Our results indicate metformin to be effective for HbA(1c) improvement in subjects with a low L/A. In conclusion, we demonstrate that L/A is different between male and female subjects. The correlation of L/A and GIR by the euglycemic hyperinsulinemic clamp test suggests that L/A is a useful indicator for the choice of drug to treat diabetes mellitus.

Seasonal changes of serum 25-hydroxyvitamin D and intact parathyroid hormone levels in a normal Japanese population

We conducted an observational study in order to assess the prevalence of hypovitaminosis D and its seasonal changes, in the Tokai area (N35.3 E137.0), in 197 normal subjects in Japan. The mean serum 25-hydroxyvitamin D (25-OHD) level measured by direct radioimmunoassay (RIA) was lowest at the end of winter, and highest at the end of summer (15.1 ± 7.1 ng/ml in March; 21.5 ± 5.5 ng/ml in June; 31.6 ± 5.6 ng/ml in September; 23.1 ± 5.3 ng/ml in December; mean ± SD). The prevalence of hypovitaminosis D (<20 ng/ml) was 86.7%, 33.4%, 1.0%, and 26.0% in March, June, September, and December, respectively. Mean plasma intact parathyroid hormone (iPTH) concentration was lowest at the end of summer and highest at the end of winter (28.2 ± 9.3 pg/ml in March; 21.7 ± 7.0 pg/ml in June; 19.8 ± 6.9 pg/ml in September; and 25.7 ± 9.2 pg/ml in December; mean ± SD). Serum 25-OHD was inversely associated with iPTH (coefficient, −0.223; r = 0.251; P < 0.001). Serum 25-OHD levels were higher in men than in women. The serum 25-OHD level was positively associated with age, body weight, and body mass index, but not with body fat content. These results suggest a high prevalence of hypovitaminosis D associated with elevation of iPTH in Japan, in winter, even in a sunny area.

The therapeutic effect of lipo PGE1 on diabetic neuropathy-changes in endothelin and various angiopathic factors.

A high blood concentration of endothelin (ET)-1 may participate in the onset and progress of diabetic microangiopathy, resulting in neuropathy. We examined the therapeutic effects of prostaglandin E1 (PGE1), which possesses both a peripheral vasodilating action and inhibition of platelet aggregation, on diabetic microangiopathy. Increases in both skin temperature and peripheral never conduction velocity in diabetic patients were recorded four weeks after Lipo PGE1 administration. A quantitative decrease in urinary albumin concentration was also observed, suggesting its efficacy of action was on diabetic nephropathy. Lipo PGE1 administration reduced the elevated circulating plasma ET-1 levels in the diabetic patients. As an increase in ET-1 concentrations is thought to correlate with the onset and progress of diabetic microangiopathy, the reduction of plasma ET-1 concentration by Lipo PGE1 administration may be one reason for the improvement in diabetic neuropathy and nephropathy.

The effects of CD40‐ and interleukin (IL‐4)‐activated CD23+ cells on the production of IL‐10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

The possible roles of CD8+ cells in the abnormal T cell‐dependent B‐cell activation in Graves’ disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL‐10 in patients with Graves’ disease, Hashimoto’s thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8‐depleted cells by magnetic separation columns, and cultured for 7 days with or without anti‐CD40 monoclonal antibodies and IL‐4. The culture supernatant was assayed for sCD23 and IL‐10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti‐CD40 antibody together with IL‐4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL‐10 by PBMC from patients with Graves’ disease. The CD40‐ and IL‐4‐activated production of IL‐10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL‐10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell‐dependent B‐cell activation via a CD40 pathway activates CD23+ cells, leading to over‐production of IL‐10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves’ disease.

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B

Aims  A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported.