The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

Effects of a new 75 g glucose- and high fat-containing cookie meal test on postprandial glucose and triglyceride excursions in morbidly obese patients.

A new meal tolerance test (MTT) using a 75 g glucose- and high fat-containing meal was applied to classify glucose intolerance in morbidly obese patients. According to the MTT data, the concordance rate of diagnosis was 82.5% compared to the 75 g oral glucose tolerance test (OGTT) in patients with normal glucose tolerance (NGT, n = 40). In the NGT patients, the insulinogenic index (r = 0.833), Matsuda index (r = 0.752), and disposition index (r = 0.845) calculated from the MTT data were each significantly (p < 0.001) correlated with those derived from the OGTT data. However, in patients with impaired glucose tolerance (IGT, n = 23) or diabetes mellitus (DM, n = 17), the postprandial glucose levels post-MTT were significantly lower than those post-OGTT, without increases in the postprandial insulin levels post-MTT. Thus, the severity of glucose intolerance measured by the MTT was milder than that indicated by the OGTT. Plasma levels of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were increased at the postprandial state, but only the GIP levels post-MTT were significantly higher than those post-OGTT. The enhancement of glucose disposal rates in patients with NGT or IGT after the MTT was associated with increased GIP levels. The postprandial hypertriglyceridemia induced by the MTT was associated with insulin resistance, but it was not associated with the impaired insulinogenic index or the disposition index. These results indicate that the new MTT is clinically useful to evaluate both abnormal glucose and triglyceride excursions caused by abnormal insulin sensitivity and secretions of insulin and gut hormones in morbidly obese patients.

A Prospective, Open-Label Short-Term Pilot Study on Modification of the Skin Hydration Status During Treatment With a Sodium-Glucose Cotransporter-2 Inhibitor.

INTRODUCTION: Various types of skin lesions with pruritus have been reported in participants of Asian clinical trials on sodium-glucose cotransporter-2 (SGLT2) inhibitors. The aim of this study was to determine whether the diuretic effect of a SGLT2 inhibitor could modify skin hydration status in patients with type 2 diabetes mellitus. METHODS: A prospective, short-term, open-label, two-parallel-arm, pilot study was conducted. Eligible patients were assigned to either a SGLT2 inhibitor (50 mg ipragliflozin once daily) group or to a dipeptidyl peptidase-4 inhibitor (50 mg sitagliptin once daily) group (control). The biophysical characteristics of the skin were measured and blood chemistry tests were run in all participants 1 day prior to medication initiation (pre-treatment values) and 14 days thereafter (post-treatment values). RESULTS: Fourteen patients were enrolled in the study, of whom eight were in the ipragliflozin group and six in the sitagliptin group. Compared to the pre-treatment values, the glycated hemoglobin (HbA1c) levels were slightly but significantly reduced in the ipragliflozin group (p = 0.02), but the changes in HbA1c from the pre-treatment to post-treatment time points did not significantly differ between the two treatment groups. Serum 3-hydroxy butyrate levels were significantly higher in the ipragliflozin group than in the sitagliptin group (p < 0.02). Neither electrical capacitance nor electrical conductance of the stratum corneum (SC), parameters that reflect skin water content, was reduced by 14 days of ipragliflozin treatment; similarly, no changes in these parameters were found in the sitagliptin control group. There was also no difference in the changes in water barrier function of the SC between the two treatment groups. There was a significant linear correlation (p < 0.01) in skin water content at pre-treatment and that 14 days after treatment with each drug, respectively. CONCLUSION: Ipragliflozin treatment for 14 days did not significantly affect the skin hydration status in patients with well-controlled type 2 diabetes mellitus.

Observation of p.R4810K, a Polymorphism of the Mysterin Gene, the Susceptibility Gene for Moyamoya Disease, in Two Female Japanese Diabetic Patients with Familial Partial Lipodystrophy 1.

Mysterin, which was recently shown to play an important role in maintaining cellular fat storage, has been identified to be the susceptibility gene for moyamoya disease (MMD). We encountered some female Japanese patients with partial lipodystrophy and MMD-like vascular lesions. This prompted us to examine whether mysterin variants may be present in these patients. We identified a mysterin variant, p.R4810K in two patients with MMD-like vascular lesions, who may fit the category of familial partial lipodystrophy (FPLD) 1. Our cases suggest the possibility that p.R4810K, in addition to atherogenic risk factors, might thus play a role in the development of atherosclerotic lesions in patients with FPLD1 and p.R4810K.

Clinical characteristics in two patients with partial lipodystrophy and Type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.

AIMS: The present report aimed to clarify the clinical characteristics in a girl at the age of 12 and her mother with partial lipodystrophy and Type A insulin resistance syndrome. METHODS: We examined fat distribution in the patients using dual-energy X-ray absorptiometry, magnetic resonance imaging, and computed tomography. We performed genetic analysis to examine the causal gene for lipodystrophy and insulin resistance. RESULTS: Both patients had partial lipodystrophy and a novel heterozygous missense mutation (Asn1137 → Lys1137) in the insulin receptor gene. Because Asn1137 in the catalytic loop is conserved in all protein kinases, this mutation was thought to impair insulin receptor function. By whole-exome sequencing, we found the proband had neither mutations in candidate genes known to be associated with familial partial lipodystrophy nor novel likely candidate causal genes. Taken together, we thought that fat loss in these two patients might be caused by insulin receptor dysfunction. The proband had amenorrhea due to polycystic ovary syndrome. Her menstruation improved, as fat loss was restored during adolescence. This might be caused by improving insulin resistance due to increased levels of leptin and fat mass. CONCLUSIONS: This case might help to understand the mechanisms insulin receptor dysfunction that cause lipodystrophy.