Comparative risks of diabetes-related complications of basal insulins: a longitudinal population-based cohort of type 1 diabetes 1999-2013 in Taiwan.

AIM: We compared the effects of two types of basal insulin: long-acting insulin analogues vs. intermediate/long-acting human insulin, on diabetes-related complications in type 1 diabetes. METHODS: A total of 1188 patients with type 1 diabetes who had recently started on long-acting insulin analogues or intermediate/long-acting human insulin were identified in 2004-2008 and followed until death or the end of 2013. Clinical outcomes included acute (i.e. hyperglycaemia, hypoglycaemia) and chronic (i.e. nephropathy, retinopathy, neuropathy, cardiovascular diseases) complications. Diabetes-related complications were measured as a composite outcome which included acute and chronic complications. Cox proportional hazards models were used to assess the time to event hazard ratio. Three propensity score (PS) methods were applied to adjust for baseline imbalances between basal insulin groups, including the PS-matching approach (as the main analysis), standardized mortality ratio weighting (SMRW) and inverse probability of treatment weighting (IPTW). RESULTS: Long-acting insulin analogues vs. intermediate/long-acting human insulin had a lower risk for a composite of diabetes-related complications {adjusted hazards ratios [aHRs] [95% confidence interval (CI)] 0.782 [0.639, 0.956], 0.743 [0.598, 0.924] and 0.699 [0.577, 0.846] according to the PS-matching approach, SMRW and IPTW, respectively}. Compared with intermediate/long-acting human insulin, using long-acting insulin analogues had a lower hypoglycaemia risk: aHRs (95% CI) 0.681 (0.498, 0.930), 0.662 (0.466, 0.943) and 0.639 (0.471, 0.867) from the PS-matching approach, SMRW and IPTW, respectively. No statistical differences were found between two types of insulin on individual chronic complications. CONCLUSION: A trend of lower diabetes-related complications associated with long-acting insulin analogues vs. intermediate/long-acting human insulin was observed. A reduced hypoglycaemia risk with long-acting insulin analogues was confirmed in this 'real-world' study.

BMI Trajectories as a Harbinger of Pre-Diabetes or Underdiagnosed Diabetes: an 18-Year Retrospective Cohort Study in Taiwan.

BACKGROUND: Although prior studies have examined BMI trajectories in Western populations, little is known regarding how BMI trajectories in Asian populations vary between adults with and without diabetes. OBJECTIVE: To examine how BMI trajectories vary between those developing and not developing diabetes over 18 years in an Asian cohort. DESIGN: Multilevel modeling was used to depict levels and rates of change in BMI for up to 18 years for participants with and without self-reported physician-diagnosed diabetes. PARTICIPANTS: We used 14,490 data points available from repeated measurements of 3776 participants aged 50+ at baseline without diabetes from a nationally representative survey of the Taiwan Longitudinal Study on Aging (TLSA1989-2007). MAIN MEASURES: We defined development of diabetes as participants who first reported diabetes diagnoses in 2007 but had no diabetes diagnoses at baseline. We defined the reference group as those participants who reported the absence of diabetes at baseline and during the entire follow-up period. KEY RESULTS: When adjusted for time-varying comorbidities and behavioral factors, higher level and constant increases in BMI were present more than 6.5 years before self-reported diabetes diagnosis. The higher BMI level associating with the development of diabetes was especially evident in females. Within 6.5 years prior to self-reported diagnosis, however, a wider range of decreases in BMI occurred (ßdiabetes = 1.294, P = 0.0064; ßdiabetes*time = 0.150, P = 0.0327; ßdiabetes*time (2) = -0.008, P = 0.0065). The faster rate of increases in BMI followed by a greater decline was especially prominent in males and individuals with BMI ≧24. CONCLUSIONS: An unintentional decrease in BMI in sharp contrast to the gradually rising BMI preceding that time may be an alarm for undiagnosed diabetes or a precursor to developing diabetes.

A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

The Serum Concentrations of Hedgehog-Interacting Protein, a Novel Biomarker, Were Decreased in Overweight or Obese Subjects.

Although it was known that obesity is an independent risk factor for metabolic disorders including diabetes, the factors that link these diseases were obscure. The Hedgehog-interacting protein (Hhip) is a negative regulator in tissue remodeling, and inhibits the proliferation of adipocytes, and promotes their differentiation. In addition, Hhip was positively associated with diabetes. However, the relationship between Hhip and obesity in the human body remains unclear. An analysis of the relationship between Hhip and normal weight, overweight, and obesity levels. Participants receiving a physical checkup were recruited. Anthropometric and biochemical data were collected. Serum Hhip levels were determined by enzyme-linked immunosorbent assay (ELISA). Subjects were classified into normal-weight, overweight, and obese groups based on their body mass index (BMI). The association between Hhip and obesity was examined by multivariate linear regression analysis. In total, 294 subjects who were either of a normal weight (n = 166), overweight (n = 90), or obese (n = 38) were enrolled. Hhip concentrations were 6.51 ± 4.86 ng/mL, 5.79 ± 4.33 ng/mL, and 3.97 ± 3.4 ng/mL in normal-weight, overweight, and obese groups, respectively (p for trend = 0.032). Moreover, the regression analysis showed that BMI (ß = -0.144, 95% confidence interval (CI) = -0.397-0.046, p = 0.013) was negatively associated with Hhip concentrations after adjusting for sex and age. Being overweight (ß = -0.181, 95% CI = -3.311-0.400, p = 0.013) and obese (ß = -0.311, 95% CI = -6.393-2.384, p < 0.001) were independently associated with Hhip concentrations after adjusting for sex, age, fasting plasma glucose, the insulin level, and other cardiometabolic risk factors. Our results showed that overweight and obese subjects had lower Hhip concentrations than those of normal weight. Being overweight and obese were negatively associated with Hhip concentrations. Hhip might be a link between obesity and diabetes.

Comparing a Social and Communication App, Telephone Intervention, and Usual Care for Diabetes Self-Management: 3-Arm Quasiexperimental Evaluation Study.

BACKGROUND: Many technology-assisted innovations have been used to manage disease. However, most of these innovations are not broadly used by older adults due to their cost. Additionally, disease management through technology-assisted innovations has not been compared with other interventions. OBJECTIVE: In this study, we tested the employment of a free and widely used social and communication app to help older adults with diabetes manage their distress and glycemic control. We also compared the effectiveness of the app with 2 other methods, namely telephone and conventional health education, and determined which subgroup experiences the most effects within each intervention. METHODS: Adults aged ≥50 years with type 2 diabetes were recruited from Southern Taiwan (N=231) and were allocated to different 3-month interventions. Informed consent was obtained at the Ministry of Science and Technology and approved by the National Cheng Kung University Hospital Institutional Review Board (No. A-ER-102-425). RESULTS: Participants in the mobile-based group had significant reductions in hemoglobin A1c compared with the telephone-based and usual care groups (mean changes of -0.4%, 0.1%, and 0.03%, respectively; P=.02). Diabetes-specific distress decreased to a greater extent in the mobile-based group compared to the other 2 groups (mean changes of -5.16, -3.49, and -2.44, respectively, P=.02). Subgroup analyses further revealed that the effects on reducing blood glucose levels in the social and communication app groups were especially evident in patients with lower distress scores, and diabetes-related distress was especially evident in participants who were younger than 60 years or had higher educational levels. CONCLUSIONS: The findings of this study inform more flexible use of social and communication apps with in-person diabetes education and counselling.

Discovery of a role of the novel hepatokine, hepassocin, in obesity.

Obesity is a public health problem that has raised concerns worldwide and is often associated with hepatic steatosis. Hepassocin is a novel hepatokine that causes hepatic steatosis and induces insulin resistance (IR). However, the role of hepassocin in obesity remains obscure. Thus, the aim of this study was to investigate the relationship between hepassocin levels and obesity. In total, 371 subjects who had a normal weight (NW), were overweight, or were obese were enrolled. We found that hepassocin levels in subjects who were overweight (6,705 ± 1,707 pg/ml) or obese (7,335 ± 2,077 pg/ml) were significantly higher than those of subjects with a NW (5,767 ± 1,500 pg/ml) (p < .001, test for trend). A multiple linear regression analysis showed that the body-mass index, waist circumference, nonalcoholic fatty liver disease, and homeostatic model assessment of IR were independently associated with hepassocin after adjusting for age, sex, high-sensitivity C-reactive protein, systolic blood pressure, high-density lipoprotein-cholesterol, log triglycerides, alanine transaminase, and the estimated glomerular filtration rate. This study provides evidence that subjects who were overweight or obese had significantly higher hepassocin levels than those with a NW. Hepassocin may be a useful biomarker in managing obesity and its related metabolic dysregulation.

Longitudinal investigation of the reciprocal relationship between depressive symptoms and glycemic control: The moderation effects of sex and perceived support.

AIMS/INTRODUCTION: The present study investigated the longitudinal associations between depressive symptoms and glycemic control in nationally representative adults with type 2 diabetes, and tested the effects of sex and perceived family support in moderating this association. MATERIALS AND METHODS: In this longitudinal study of middle-aged and older adults who participated in the 2002 and 2006 Health and Retirement Study, and the 2003 and 2006 Diabetes Study (n = 398), we applied a cross-lagged structural equation model to examine the reciprocal relationship between depressive symptoms and glycemic control over a 3-year period. RESULTS: Men and women were not different in terms of the depressive symptoms and glycemic control relationship, with a stronger association noted for higher depressive symptom scores predicting worse glycemic control (ß = 0.22, critical ratio 3.03), as opposed to worse glycemic control predicting higher depressive symptom scores. Family and friend support for diabetes self-management serves as an important buffer. In patients with low family and friend support, more depressive symptoms at baseline were associated with subsequent worse glycemic levels (ß = 0.36, critical ratio 4.03). In contrast, in individuals who had strong support, depressive symptoms did not predict subsequent glycemic control. CONCLUSIONS: The present study provided evidence for the relationship between glycemic control and depression, finding that depressive symptoms predicted poorly controlled glycemic status, especially when the participants perceived inadequate support from their family or friends. A quick survey in clinics to assess the level of family or friend support for diabetes management and depressive symptoms might be an important part of individualized diabetic care.

Impact of New Technologies for Middle-Aged and Older Patients: In-Depth Interviews With Type 2 Diabetes Patients Using Continuous Glucose Monitoring.

BACKGROUND: Continuous glucose monitoring (CGM) uses subcutaneous sensors and records the average interstitial sensor current every 5 min in the recorder; data are subsequently exported to a computer 4 to 7 days later when calibration with self-measured blood glucose is made retrospectively. How middle-aged and older patients perceive the added technology intervention is not clear. OBJECTIVE: The study aimed to understand the factors associated with the adoption of new technology in diabetes care, to understand the feelings and behaviors while using it, and to determine the changes in attitudes and behavior after completing the use of the new technology at the 3-month follow-up. METHODS: Middle-aged and older type 2 diabetes patients who had received professional continuous glucose monitoring (iPro 2 [Medtronic]) were invited for semistructured in-depth interviews on the day of the CGM sensor removal and at 3 months after CGM-based counseling. A phenomenography approach was used to analyze the interview data. RESULTS: A total of 20 type 2 diabetes patients (aged 53 to 72 years, 13 males and 7 females, 4 to 40 years duration of diabetes, mean glycated hemoglobin 8.54% [SD 0.71%]) completed 2 sections of semistructured in-depth interviews. Physician guidance and participant motivation toward problem solving were found to be factors associated with adoption of the device. Participants indicated that technology can be a reminder, a supervisor, and a visualizer of blood glucose, all of which are helpful for disease management. However, CGM is somewhat inconvenient, and some participants also reported that the provision of this new technology might be a hint of disease progression. There was a higher percentage of women compared with men who reported that CGM can be a reminder or a supervisor to help them with diet control. CONCLUSIONS: Physician guidance and participants' degree of motivation are keys to adopting new technology in the case of middle-aged and older adults. Although the CGM sensor may cause inconvenience to patients on their limited body movement when wearing the device, it is helpful for diet control and is an effective behavioral modification tool that offers support, especially in the case of women.

The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis.

Context: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown. Objective: To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis. Design, Setting, and Patients: Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression. Results: Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability. Conclusions: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.

Fenretinide inhibits macrophage inflammatory mediators and controls hypertension in spontaneously hypertensive rats via the peroxisome proliferator-activated receptor gamma pathway.

Fenretinide is a novel anticancer agent reported to exhibit anti-invasive and antimetastatic activities. It has also been shown to improve obesity and diabetes, although the effects of fenretinide on hypertension are still unknown, and the detailed mechanisms remain unclear. In this study, we have shown that treatment with lipopolysaccharide (LPS) decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in RAW264.7 macrophages, and pretreatment with fenretinide reversed the effect of LPS on PPARγ expression. In addition, LPS-induced pro-inflammatory cytokine production, including tumor necrosis factor-α, interleukin 6, and monocyte chemoattractant protein 1 were dose-dependently reversed by fenretinide, and the effects of fenretinide on LPS-induced pro-inflammatory cytokine production were blocked by treatment with PPARγ antagonist. Moreover, fenretinide decreased LPS-induced inducible nitric oxide synthase expression and nitrogen oxide production. These effects were blocked by the pretreatment with PPARγ antagonist in a dose-dependent manner, indicating fenretinide activated PPARγ to exert anti-inflammation activity. In view of the role of inflammation in hypertension and the anti-inflammatory action of fenretinide, we found that administration of fenretinide in spontaneously hypertensive rats significantly decreased blood pressure. Taken together, these results indicate that fenretinide might be a potent antihypertensive agent that works by suppressing inflammation via activating PPARγ.

Achieving glycemic control in elderly patients with type 2 diabetes: a critical comparison of current options.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the elderly. Because of the unique characteristics of elderly people with T2DM, therapeutic strategy and focus should be tailored to suit this population. This article reviews the guidelines and studies related to older people with T2DM worldwide. A few important themes are generalized: 1) the functional and cognitive status is critical for older people with T2DM considering their life expectancy compared to younger counterparts; 2) both severe hypoglycemia and persistent hyperglycemia are deleterious to older adults with T2DM, and both conditions should be avoided when determining therapeutic goals; 3) recently developed guidelines emphasize the avoidance of hypoglycemic episodes in older people, even in the absence of symptoms. In addition, we raise the concern of glycemic variability, and discuss the rationale for the selection of current options in managing this patient population.