Positive association between the proinsulin-to-C-peptide ratio and prolonged hyperglycemic time in type 2 diabetes

The proinsulin-to-C-peptide (PI:C) ratio is an index applied during the early stage of pancreatic β-cell dysfunction. The aim of this study was to identify the characteristics associated with the PI:C ratio to discuss pancreatic β-cell dysfunction progression during the natural course of type 2 diabetes and its relationship with glycemic management. This multicenter, prospective observational study included 272 outpatients with type 2 diabetes. Continuous glucose monitoring was performed and fasting blood samples were collected and analyzed. We identified the clinical factors associated with the PI:C ratio by multiple regression analysis. The mean age of the cohort was 68.0 years, mean hemoglobin A1c 7.1% (54 mmol/mol), and mean body mass index 24.9 kg/m2. Multiple regression analysis showed that a prolonged time above the target glucose range (>180 mg/dL) and high body mass index contributed to a high PI:C ratio. However, no associations were found between the PI:C ratio and glucose variability indices. These findings suggested that the PI:C ratio is positively associated with a prolonged hyperglycemic time in type 2 diabetes, whereas its relationship with glucose variability remains unclear

Beneficial effects of switching to denosumab from bisphosphonates or selective estrogen receptor modulators in postmenopausal women with type 2 diabetes and osteopenia/osteoporosis

Aims/Introduction Patients with type 2 diabetes mellitus have a higher bone fracture risk than patients without diabetes. Although denosumab (Dmab) is a potent bone resorption inhibitor, its efficacy in patients with type 2 diabetes mellitus has not been elucidated. In this study, we investigated the effects of switching to Dmab from bisphosphonates (BP) or a selective estrogen receptor modulator (SERM) in postmenopausal type 2 diabetes mellitus patients. Materials and Methods This was a three medical institutions, prospective, observational study for postmenopausal patients with type 2 diabetes mellitus whose T‐score of femoral neck or lumbar spine bone mineral density was under -1.0 standard deviation, even after >6 months of BP or SERM administration. After obtaining consent, participants were treated for osteopenia/osteoporosis by either continuing BP (BP‐BP group)/SERM (SERM‐SERM group), or by switching to Dmab (BP‐Dmab or SERM‐Dmab groups). Changes in bone mineral density and bone metabolism marker levels were evaluated after 6 months. Results A total of 48 patients were included in this study, and each group comprised 12 patients. No significant difference existed in baseline characteristics among the groups. The average age and glycated hemoglobin were 71 ± 8 years and 7.2 ± 0.9%, respectively. In the SERM‐Dmab group, lumbar spine bone mineral density was significantly increased by 5.0% compared with the SERM‐SERM group (P < 0.04). Serum bone‐specific alkaline phosphatase and tartrate‐resistant acid phosphatase 5b were significantly decreased in the BP‐Dmab and SERM‐Dmab groups compared with the BP‐BP and SERM‐SERM groups, respectively. Conclusions Switching to Dmab from BP or SERM is beneficial to prevent osteoporosis progression in postmenopausal patients with type 2 diabetes mellitus patients

Impact of Glucose Loading on Variations in CD4+ and CD8+ T Cells in Japanese Participants with or without Type 2 Diabetes

Objective: The aim of this study was to examine the fluctuations in CD4+ T cells, CD8+ T cells, and natural CD4+CD25+FoxP3+T-regulatory (Treg) cells following an oral glucose tolerance test (OGTT) in participants with and those without type 2 diabetes (T2DM). Methods: 19 Japanese participants with T2DM (DM group) and 21 participants without diabetes (non-DM group) were recruited and underwent a 75-g OGTT. The cell numbers of leukocytes, lymphocytes, and the T cell compartment, such as CD4+, CD8+, and Treg, were calculated for blood samples obtained after an overnight 12 h fast and during a 75-g OGTT at 60 and 120 min. Results: Before glucose loading, no differences in the cell numbers of leukocytes, lymphocytes, CD4+, CD8+, and Treg were observed between the DM group and the non-DM group. The proportion of CD8+ was significantly reduced, whereas the proportion of CD4+ was significantly increased, after 120 min of glucose loading in both groups. The proportion of Treg was not affected. Furthermore, a significant positive correlation was observed between the AUC0-120 min of CD8+ and the change in the free fatty acid level following the OGTT (ρ = 0.39, P < 0.05), but not that of glucose or insulin. Conclusion: The proportion of CD4+ T cells was increased and that of CD8+ T cells was reduced after glucose loading in both subjects with and without diabetes. These findings suggest that glucose loading dynamically affects the balance of the circulating T lymphocyte subset, regardless of glucose tolerance

Gitelman's syndrome with hyperphosphatemia, effectively responding to single oral magnesium oxide administration A case report

Rationale: The Gitelman's syndrome (GS) is characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. However, the involvement of this deranged electrolyte balance in patients with GS in parathyroid hormone action has not been known. Patient concerns: We report a 34-year-old woman with muscle weakness and tetany/seizures caused by electrolyte imbalance. She had hyperphosphatemia and hypocalciuric hypocalcemia in addition to severe hypomagnesemia with low potassium in the absence of metabolic alkalosis. We identified 2 heterozygous mutations in the solute carrier family 12 member 3 gene in this case (c.1732G>A, p.Val578Met and c.2537_38delTT, p.846fs) by targeted sequence for all causative genes of salt-losing tubulopathies. Diagnoses: A diagnosis of GS. Hypocalcemia and hyperphosphatemia were suggested to relate with the secondary obstruction of appropriate parathyroid hormone release following severe hypomagnesemia in GS. Interventions: She was treated with single oral magnesium oxide administration. Outcomes: The electrolyte imbalance including hypocalcemia and hyperphosphatemia were resolved with a remission of clinical manifestations. Lessons: These observations, in this case, suggest that even severe hypomagnesemia caused by GS was associated with resistance to appropriate parathyroid hormone secretion. Through this case, we recognize that secondary hypoparathyroidism would be triggered by severe hypomagnesemia in GS

Correlation between serum proinsulin levels and fatty liver : The Dynamics of Lifestyle and Neighborhood Community on Health Study Health Study

Aims/Introduction We explored the association between fatty liver and pancreatic beta-cell dysfunction in a general population. Materials and Methods This cross-sectional study included 489 (53.8% women) community-dwelling Japanese adults. The extent of fatty liver was estimated using the fatty liver index (FLI). After all participants were divided into three groups - low (FLI = 60) degree of fatty liver - serum proinsulin levels transformed into natural logarithms were compared among the three groups. To determine whether obesity modified the association of interest, the participants were stratified into two groups according to the median body mass index. Next, to determine whether hyperinsulinemia modified the association of interest, a similar stratified analysis was carried out using the median serum insulin level. Results Logarithm (proinsulin) was significantly higher in the high FLI group than in the moderate and low groups, and it was significantly higher in the moderate group than in the low group after adjustment for age and sex (P < 0.05). Logarithm (proinsulin) was significantly higher in the high FLI group than in the low FLI group, regardless of body mass index, after adjustment for age and sex. A similar pattern was observed regardless of serum insulin levels. Conclusions The degree of fatty liver was positively associated with proinsulin level, regardless of the presence of obesity or hyperinsulinemia, suggesting that fatty liver reflects pancreatic beta-cell dysfunction

Glucose tolerance is improved following surgery for silent somatotroph adenoma

Although the excessive secretion of GH leads to insulin resistance enhancement, the involvement of a silent somatotroph adenoma in abnormal glucose tolerance has not been elucidated. A 50 - year-old man was admitted with a headache and bitemporal hemianopia caused by a pituitary macroadenoma. He had no physical signs and symptoms of acromegaly nor hypopituitarism, and his base-line serum levels of GH and insulin - like growth factor-1 (IGF-1) were normal. However, a 75 - g oral glucose tolerance test (OGTT) showed unsuppressed GH concentrations as well as plasma glucose levels consistent with diabetes pattern. A transsphenoidal adenomectomy was performed, and we diagnosed the patient as having a silent somatotroph adenoma based on positive GH in the immunohistochemistry. Postoperative OGTT showed GH suppression and a normal pattern of plasma glucose levels after glucose loading. The post-surgery homeostasis model assessment insulin resistance index (HOMA - IR) and the Matsuda Index indicated improved insulin sensitivity in the absence of perioperative body-mass-index change. These observations suggest that reversible abnormal glucose tolerance is associated with a silent somatotroph adenoma in this patient

Beneficial effects of switching to denosumab from bisphosphonates or selective estrogen receptor modulators in postmenopausal women with type 2 diabetes and osteopenia/osteoporosis

AIMS/INTRODUCTION: Patients with type 2 diabetes mellitus have a higher bone fracture risk than patients without diabetes. Although denosumab (Dmab) is a potent bone resorption inhibitor, its efficacy in patients with type 2 diabetes mellitus has not been elucidated. In this study, we investigated the effects of switching to Dmab from bisphosphonates (BP) or a selective estrogen receptor modulator (SERM) in postmenopausal type 2 diabetes mellitus patients. MATERIALS AND METHODS: This was a three medical institutions, prospective, observational study for postmenopausal patients with type 2 diabetes mellitus whose T‐score of femoral neck or lumbar spine bone mineral density was under −1.0 standard deviation, even after >6 months of BP or SERM administration. After obtaining consent, participants were treated for osteopenia/osteoporosis by either continuing BP (BP‐BP group)/SERM (SERM‐SERM group), or by switching to Dmab (BP‐Dmab or SERM‐Dmab groups). Changes in bone mineral density and bone metabolism marker levels were evaluated after 6 months. RESULTS: A total of 48 patients were included in this study, and each group comprised 12 patients. No significant difference existed in baseline characteristics among the groups. The average age and glycated hemoglobin were 71 ± 8 years and 7.2 ± 0.9%, respectively. In the SERM‐Dmab group, lumbar spine bone mineral density was significantly increased by 5.0% compared with the SERM‐SERM group (P < 0.04). Serum bone‐specific alkaline phosphatase and tartrate‐resistant acid phosphatase 5b were significantly decreased in the BP‐Dmab and SERM‐Dmab groups compared with the BP‐BP and SERM‐SERM groups, respectively. CONCLUSIONS: Switching to Dmab from BP or SERM is beneficial to prevent osteoporosis progression in postmenopausal patients with type 2 diabetes mellitus patients