Jeong-Ah Shin

Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness.

Metabolic syndrome is defined as a cluster of glucose intolerance, hypertension, dyslipidemia and central obesity with insulin resistance as the source of pathogenesis. Although several different combinations of criteria have been used to define metabolic syndrome, a recently published consensus recommends the use of ethnic‐specific criteria, including waist circumference as an indicator of central obesity, triglyceride and high‐density lipoprotein (HDL) cholesterol as indicators of dyslipidemia, and blood pressure greater than 130/85 mmHg. The definition of dysglycemia, and whether central obesity and insulin resistance are essential components remain controversial. Regardless of the definition, the prevalence of metabolic syndrome is increasing in Western and Asian countries, particularly in developing areas undergoing rapid socioenvironmental changes. Numerous clinical trials have shown that metabolic syndrome is an important risk factor for cardiovascular disease (CVD), type 2 diabetes mellitus and all‐cause mortality. Therefore, metabolic syndrome might be useful as a practical tool to predict these two major metabolic disorders. Comprehensive management of risk factors is very important to the improvement of personal and public health. However, recent studies have focused on the role metabolic syndrome plays as a risk factor for CVD; its importance in the prediction of incident diabetes is frequently overlooked. In the present review, we summarize the known evidence supporting metabolic syndrome as a predictor for type 2 diabetes mellitus and CVD. Additionally, we suggest how metabolic syndrome might be useful in clinical practice, especially for the prediction of diabetes.

A comparative study of the effects of a dipeptidyl peptidase-IV inhibitor and sulfonylurea on glucose variability in patients with type 2 diabetes with inadequate glycemic control on metformin.

BACKGROUND This study aimed to compare the effects of sitagliptin on glycemic change and 24-h blood glucose variability with those of the sulfonylurea glimepiride. SUBJECTS AND METHODS A 4-week randomized double blind-labeled prospective design was used. We recruited 33 patients who had been treated with metformin for at least 2 months. Each participant prescribed with metformin was randomly assigned to either the sitagliptin (100 mg) or the glimepiride (2 mg) group. Continuous glucose monitoring (CGM) was used to monitor glycemic changes for 3 successive days in both groups at baseline and at the 4-week follow-up. Glycemic changes and glucose variability were obtained using CGM, and these data were averaged over all subjects. RESULTS The comparison of glycated hemoglobin (HbA1c) between baseline and the 4-week follow-up showed that HbA1c was significantly reduced in the sitagliptin group (7.0 ± 0.5% to 6.6 ± 0.4%, P<0.001) and the glimepiride group (7.3 ± 0.4% to 6.9 ± 0.4%, P<0.001). The sitagliptin and glimepiride groups had similar HbA1c levels after 4 weeks, and there were no significant differences between the two groups. The mean amplitude of glycemic excursions (MAGE) decreased significantly in the sitagliptin group (4.9 ± 1.0 to 3.7 ± 0.9 mmol/L, P<0.001), but no significant difference was observed in the glimepiride group (5.7 ± 1.5 to 5.0 ± 1.4 mmol/L, P=0.175). The SD and oxidative stress markers did not differ significantly between the two groups. CONCLUSIONS When sitagliptin was combined with metformin, the patients showed much more efficient blood glucose controlling effects, not only the three indexes of fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, but also MAGE.

Prevention of diabetes: a strategic approach for individual patients.

The ‘diabetes epidemic’ is an important health and socioeconomic problem worldwide. Type 2 diabetes is a chronic disease with gradual deterioration in glucose metabolism which causes multiple systemic complications. Therefore, early intervention in the prediabetic stage is a valuable approach to reduce diabetes development and related complications. Many clinical trials have suggested that lifestyle intervention, including moderate‐intensity exercise and diet control, and pharmacologic intervention using metformin, α‐glucosidase inhibitors, thiazolidinediones, anti‐obesity drugs and incretin mimics, are effective in preventing diabetes development. However, an individualized approach with careful consideration of the patient’s risk status and health economics is needed to perform a successful intervention programmes. In this review, we will summarize the known evidence on treatment‐ and cost‐effectiveness of drug and lifestyle treatment. Additionally, we will propose a strategic approach algorithm that is applicable to clinical practice.

β-cell mass in people with type 2 diabetes.

The early occurrence of β‐cell dysfunction has been broadly recognized as a critical determinant of the development and progression of type 2 diabetes. β‐cell dysfunction might be induced by insufficient β‐cell mass, by a dysfunction of the β‐cells, or both. Whether or not β‐cell dysfunction constitutes a cause of reduced β‐cells or vice‐versa currently remains unclear. The results of some studies have measured the loss of β‐cells in type 2 diabetic patients at between 22 and 63% by planimetric measurements. Because β‐cell hypertrophy has been noted in type 2 diabetic patients, the loss of β‐cell number should prove more profound than what has thus far been reported. Furthermore, β‐cell volumes are reduced even in patients with impaired fasting glucose. Such defects in β‐cell mass are associated with increased apoptosis rather than insufficient replication or neogenesis of β‐cells. With these results, although they still require clarification, the peak β‐cell mass might be determined at quite an early stage of life, and then might decline progressively over time as the result of exposure to harmful environmental influences over one’s lifetime. In this review, we have summarized the relevant studies regarding β‐cell mass in patients with type 2 diabetes, and then presented a review of the various causes of β‐cell loss in adults. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00072.x, 2010)

Continuous glucose monitoring: current clinical use

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real‐time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed‐loop system have proven to be optimistic. CGM‐integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Transforming growth factor-β induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells†‡

Pancreatic duct cells are considered a potential source of β‐cell regeneration, and transforming growth factor‐β (TGF‐β) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF‐β1, pancreatic duct cells were isolated from three brain‐dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF‐β1. We analyzed the characteristics of the cultured cells, the TGF‐β1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF‐β1 treatment. After TGF‐β1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. β cell‐specific transcription factors including PDX‐1, Beta2/NeuroD, Ist‐1, and NGN3 were markedly suppressed and the rate of transdifferentiation into β cells was also suppressed. Genomic and proteomic analyses suggested that TGF‐β1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF‐β1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into β cells. Our results are the first report of TGF‐β1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells. J. Cell. Biochem. 112: 179–188, 2011.

Chorea-ballism associated with nonketotic hyperglycaemia or diabetic ketoacidosis: characteristics of 25 patients in Korea.

Chorea-ballism is a rare form of movement disorder complicated by severe hyperglycaemia and in association with a contralateral basal ganglia lesion. We analysed the clinical characteristics of 25 Korean patients with chorea-ballism associated with nonketotic hyperglycaemia or diabetic ketoacidosis. Possible mechanisms of disease are also discussed.

Urgent Need of Ubiquitous Healthcare for Chronic Disease Management: Focused on Diabetes for the First Step

Various kinds of interactive online communication systems have been introduced for diabetes management, and their importance in managing patients is increasing. Information technology should never be seen as an end in itself, but as a tool to complement other aspects of holistic patient-centered diabetes care. This work is an important corner-stone in the evolution of medicine into the new era. We believe that Ubiquitous healthcare system for chronic disease management provides a landmark in the new trend in disease management.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment

Background There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. Methods In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. Results Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. Conclusion Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes

Background The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. Methods In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. Results Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. Conclusion Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.