The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4.

Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.

[Risks of type 2 diabetes mellitus and impaired glucose regulation among elderly patients with essential hypertension: a 10-years cohort study].

OBJECTIVE: To explore the incidence of type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) among elderly patients with and without hypertension during a follow-up period of 10 years. METHODS: The subjects were elderly patients (> 60 years old) undergoing annual health examinations at our hospital. And the previously diagnosed T2DM and IGR patients were excluded. And the incidence and risk factors were analyzed by Kaplan-Meier method and COX's proportional hazard. RESULTS: Among a total of 1136 subjects, 582 were enrolled. They were divided into essential hypertension group (HT, n = 384) and non-essential hypertension group (NHT, n = 198) (including new-onset 67 subjects). During a 10-year follow-up, the incidence of new-onset diabetes was 27.6% in HT group and 18.7% in NHT group (HR = 1.48; 95%CI: (1.07 - 2.04), P < 0.05). And the incidence density of T2DM were 33.8‰ and 20.6‰ respectively in two groups. There was no difference in the prevalence of IGR among HT and NHT groups and no difference was found in the prevalence of T2DM or IGR among new-onset HT and NHT groups. The independent risk factors of T2DM was dyslipidemia (HR = 1.459; 95%CI: 1.027 - 2.072, P < 0.05) and hypertension (HR = 1.516; 95%CI: 1.039 - 2.212, P < 0.05) based upon the COX's proportional hazard analysis. Dyslipidemia (HR = 1.545; 95%CI: 1.087 - 2.195, P < 0.05) and hypertension (HR = 1.524; 95%CI: 1.044 - 2.224, P < 0.05) were also independent risk factors of abnormal glycometabolism (T2DM and IGR). Kaplan-Meier analysis indicated that the accumulative incidence of DM and abnormal glycometabolism was different between the HT and NHT groups. CONCLUSION: The DM risk is 1.516 folds higher in elderly patients with HT than in those without. According to multivariate analysis, hypertension and dyslipidemia are independent risk factors of T2DM and abnormal glycometabolism (T2DM and IGR).

Effects of a prolonged diet regimen on autophagic function in rat islets with aging.

The prevalence of type 2 diabetes increases with age-associated increased susceptibility of islet ß-cells and altered dietary patterns, in part because of insufficient compensation of ß-cell functional mass in the face of increasing insulin resistance. However, the underlying mechanisms have not been fully elucidated. In the present study, we investigated the effects of a long-term calorie-restricted (CR) or high-fat (HF) diet compared to a normal ad libitum diet on ß-cell structure-function relationships and autophagy in the islets of 3- and 24-month-old Fischer 344 rats. Aging and the HF diet decreased the ß-cell-to-islet area ratio, disorganized the islet structure, and increased the expression of senescence markers. Aging and the long-term HF diet also decreased autophagy-related proteins, which suggests compromised autophagic function. These findings were further corroborated by increased p62 accumulation and polyubiquitin aggregates observed with aging and the HF diet intervention; these are cardinal markers of attenuated autophagic function. It is important to note that the 24-month-old rats maintained on the CR diet closely mimicked the 3-month-old rats, which indicates that a long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process. Taken together, our results indicate an autophagy-dependent mechanism responsible for islet function in older people or those with altered dietary patterns and lay the foundations for future research leading to novel therapeutic strategies for treating diabetes.

[Comparison of postprandial insulin and fasting insulin on the evaluation of cardiovascular risk factors].

OBJECTIVE: To study the feasibility of using postprandial insulin (2hINS) and fasting insulin (FINS) on evaluation of insulin resistance, comparison was conducted between 2hINS and FINS on evaluation of cardiovascular risk factors. METHODS: A survey were conducted among individuals in the community in May 2008 and data of routine clinical examination were collected. All subjects were investigated and received 75 g oral glucose tolerance test (OGTT), and fasting and OGTT2 h blood glucose as well as insulin concentrations were determined. Hyperinsulinemia was defined as a FINS or 2hINS concentration at or above the 95th percentile of the distribution among normal glucose tolerance individuals. RESULTS: 1148 individuals were investigated and insulin concentration in male was similar to female. Prevalence of 2hHINS (40.8%) in individuals with abnormal glucose metabolism was higher than FHINS (18.4%, P < 0.01). The number of metabolic risk factors in subjects with 2hHINS was similar to subjects with FHINS. After adjustment by sex, age, BMI and waist circumference, partial correlation analysis showed that the correlation between 2hINS and 2hPG (r = 0.370) was higher than that of FINS and FPG (r = 0.104); FINS was higher correlated with TG and HDL- cholesterol than 2hINS, however, 2hINS was higher correlated with diastolic blood pressure, total cholesterol and LDL-cholesterol than FINS. Logistic regression analysis showed that FHINS and 2hHINS were both the independent risk factor of metabolic syndrome, the OR (95%CI) were 5.11 (2.953 - 8.842) and 3.46 (2.109 - 5.687). CONCLUSION: 2hINS and FINS were both closely associated with cardiovascular risk factors. The correlation was inconsistent when 2hINS and FINS were related to different risk factors. The combination of 2hINS and FINS might be more helpful on evaluation of insulin resistance.

[The clinical characteristics and trend of conversion to type 2 diabetes mellitus of individuals with normal glucose tolerance-hyperinsulinemia].

OBJECTIVE: To study the outcomes and influencing factors of the conversion from normal glucose tolerance-hyperinsulinemia (NGT-HINS) to diabetes in the population of a community in Beijing. METHODS: All the subjects investigated received 75 g oral glucose tolerance test (OGTT) for diabetes screening carried out in May, 2006 and May, 2008. Data were calculated to analyze the outcomes and influencing factors of the conversion. HINS was diagnosed if fasting serum insulin≥15 mIU/L and/or 2-hour serum insulin after glucose loading≥80 mIU/L. RESULTS: The prevalence of NGT-HINS in the community in 2006 and 2008 was 5.28% and 8.67% (P<0.01) respectively and that of diabetes mellitus (DM) and impaired glucose regulation (IGR) was 3.52%, 6.56% in 2006 and 4.42%, 6.47% in 2008. The probability of the conversion from NGT-HINS to IGR and DM was 18.6% and 2.3%, being much higher than that from normal glucose tolerance-normoinsulinemia (NGT-NINS) (5.4% and 0.7%, P<0.01). However, the probability of the conversion from NGT-HINS to DM was 2.3%, which was much lower than that from IGR (26.3%, P<0.01). The reason might be that individuals with NGT-HINS had a higher waist circumference, BMI, fasting plasma glucose, 2 h plasma glucose and TG but a lower HDL-C than individuals with NGT-NINS in 2006. The HOMA ß-cell function index/HOMA insulin resistance index (HBCI/IR) of individuals with NGT-HINS was much lower than that of individuals with NGT-NINS, but much higher than that of individuals with IGR. Logistic regression analysis showed that age, TG and HBCI/IR were the major influencing factors of the conversion from NGT to glucose metabolic disorders. CONCLUSIONS: The probability of conversion from NGT to DM was increased remarkably when HINS was diagnosed. The reason might be that individuals with NGT-HINS suffered more metabolic risk factors and had a decreased ß-cell function. Therefore, individuals with NGT-HINS should be paid attention to in diabetes prevention study.

Glycemic control and comprehensive metabolic risk factors control in older adults with type 2 diabetes.

BACKGROUND: Older adults with type 2 diabetes are prone to multiple metabolic abnormalities. However, data from these patients on comprehensive metabolic risk factors control are limited. METHODS: The present study included 2736 older adults aged 60 to 90 years with type 2 diabetes from 114 hospitals across 22 provinces in China. Metabolic abnormalities, including hypertension, dyslipidemia, hyperuricemia, and obesity, were recorded. Comprehensive metabolic risk factors control included the control of hemoglobin A1c (HbA1c) level, blood pressure, serum lipids level, serum uric acid level, and body mass index. The target glycemic control was defined as HbA1c <7%. RESULTS: The proportion of older adults who achieved the HbA1c target was 23.0%. The glycemic control rate increased with the number of metabolic abnormalities increased. The patients who had all four metabolic abnormalities had 4.05 times (95% confidence interval: 2.16, 7.61) the odd to meet glycemic target than those with none of metabolic abnormalities. However, only 4.6% of patients met the targets for all 5 metabolic risk factors. The comprehensive rate of all 5 factors in control decreased from 13.4% to 0% with the number of metabolic abnormalities increased. CONCLUSION: The glycemic control rate and the comprehensive metabolic risk factors control rate were 23.0% and 4.6%, respectively. As the number of metabolic abnormalities increased, the number of risk factor targets achieved decreased. Our findings suggest that a strategy for comprehensive control is urgently needed in older adults with type 2 diabetes, especially in those with co-existing metabolic abnormalities.

[Safety of metformin in the treatment of elderly type 2 diabetes mellitus].

OBJECTIVE: To evaluate the safety of metformin in the treatment of elderly type 2 diabetes mellitus (T2DM). METHODS: Two hundred and forty-three cases of elderly T2DM hospitalized from Jan. 1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. RESULTS: The mean time of treatment with metformin was (6.6 +/- 3.9) years (3 months - 21 years) in these 243 cases. The levels of FBG, PBG and HbA1c significantly reduced after treatment with metformin only in 43 cases (17.7%), metformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and metformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range (> 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr

Associations of body weight and weight change with cardiovascular events and mortality in patients with coronary heart disease.

BACKGROUND AND AIMS: It is recommended that patients with coronary heart disease (CHD) pursue a normal body weight, while the effects of body weight and weight change on prognosis are still controversial. The present study was to assess these effects using a large-scale population with CHD in China. METHODS: A total of 5276 patients with CHD were included from Jan 2000 to Dec 2014. Baseline and endpoint weights were measured. Outcomes including mortality and cardiovascular events were obtained. RESULTS: Relative to patients with normal weight, risks for adverse outcomes were lowest in overweight patients and similar in obese patients. Hazard ratios (HRs) and 95% confidence interval (95% CI) for all-cause death were 1.42 (1.06, 1.91) if overweight turned into normal weight and were 2.01 (1.28, 3.16) or 5.33 (2.81, 10.1) if obese turned into overweight or normal weight. Death risk increased with the extent of weight loss and moderate or large weight gain (p<0.05 for all). Similar results were found when risks for cardiovascular mortality and events were considered. Furthermore, these results remained significant when the patients were stratified by several covariates and even when several definitions of weight change were considered. CONCLUSIONS: Obesity did not increase adverse outcome risks in patients with CHD. Both weight loss and weight gain increased adverse outcome risks regardless of baseline body weight. The findings suggest that maintaining a stable weight may be a better strategy for the reduction of risks for cardiovascular outcomes and all-cause death in patients with CHD.

[A preliminary survey of primary hyperparathyroidism in middle-aged and elderly Beijing Chinese].

OBJECTIVE: To study the prevalence of hypercalcemia and primary hyperparathyroidism in middle-aged and elderly Chinese people who live in Beijing. METHODS: This research was performed in a large elderly population group who came to our hospital for health checkup. The medical histories and relevant data of all the subjects were collected. Serum parathyroid hormone (PTH) concentration was determined in the 83 subjects whose blood calcium level was >or= 2.6 mmol/L. Meanwhile, another 83 of the subjects whose calcium level was < 2.6 mmol/L were chosen randomly as controls. RESULTS: 2451 subjects underwent the investigation. 83 (3.39%) out of the total 2451 subjects were found to have calcium level >or= 2.6 mmol/L, and 5 of them had PTH > 65 ng/L but no causative factors for the elevation. These subjects were thought to have primary hyperparathyroidism and its prevalence was 0.204%. CONCLUSION: The prevalence of primary hyperparathyroidism was 0.204% in the investigated elderly subjects.

Clinical and pathological analysis of renal damage in elderly patients with type 2 diabetes mellitus.

The aim of this study was to investigate the causes and influential factors of renal damage in elderly patients with type 2 diabetes mellitus (T2DM). Clinical data and pathological findings at autopsy of 161 elderly T2DM patients died between October 1994 and August 2011 were retrospectively reviewed. The mean age of these patients was 80.8 ± 8.3 years (range 60-105 years). The incidences of diabetic nephropathy (DN), non-diabetic renal diseases (NDRD), and DN complicated with NDRD were 31.1, 62.7, and 16.2 %, respectively. In patients with NDRD, the incidence of hypertensive renal damage (HRD) was 54.7 %. In the factors causing renal damage, DN and NDRD accounted for 1/3 and 2/3, respectively. HRD accounted for the largest proportion of NDRD. Blood pressure control may provide additional benefits for elderly T2DM patients by preventing and delaying the occurrence and development of renal disease.

The cutoffs and performance of glycated hemoglobin for diagnosing diabetes and prediabetes in a young and middle-aged population and in an elderly population.

The aims were to compare the appropriate cutoffs of glycated hemoglobin (HbA1c) in a population of varying ages and to evaluate the performance of HbA1c for diagnosing diabetes and prediabetes. A total of 1064 participants in the young and middle-aged group and 1671 in the elderly group were included and underwent HbA1c testing and an oral glucose tolerance test (OGTT). Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated to evaluate the optimal HbA1c cutoffs. Kappa coefficients were used to test for agreement between HbA1c categorization and OGTT-based diagnoses. The optimal HbA1c cutoffs for diagnosing diabetes were 5.7% (39 mmol/mol) in the young and middle-aged group with a sensitivity of 66.7%, specificity of 86.7%, and AUC of 0.821 (95% CI: 0.686, 0.955) and 5.9% (41 mmol/mol) in the elderly group with a sensitivity of 80.4%, specificity of 73.3%, and AUC of 0.831 (0.801, 0.861). The optimal cutoffs for diagnosing prediabetes were 5.6% (38 mmol/mol) and 5.7% (39 mmol/mol) in the young and middle-aged group and in the elderly group, respectively. Agreement between the OGTT-based diagnosis of diabetes or prediabetes and the optimal HbA1c cutoff was low (all kappa coefficients <0.4). The combination of HbA1c and fasting plasma glucose increased diagnostic sensitivities or specificities. In conclusion, age-specific HbA1c cutoffs for diagnosing diabetes or prediabetes were appropriate. Furthermore, the performance of HbA1c for diagnosing diabetes and prediabetes was poor. HbA1c should be used in combination with traditional glucose criteria when detecting and diagnosing diabetes or prediabetes.

Association of calpain-10 rs2975760 polymorphism with type 2 diabetes mellitus: a meta-analysis.

Type 2 diabetes mellitus (T2DM) accounts for the majority of diabetes cases and affects a significant proportion of the adult population worldwide. Calpain-10 has been implicated in the development of type 2 diabetes, and some polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. Several molecular epidemiological studies were conducted in recent years to evaluate the association between the CAPN10 rs2975760 polymorphism and T2DM risk in diverse populations. However, the results remain conflicting rather than conclusive. We performed a meta-analysis of 8 case-control studies that included 2758 T2DM cases and 2762 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confi dence intervals (CIs). Overall, this meta-analysis showed that the CAPN10 rs2975760 polymorphism was not associated with a significantly type 2 diabetes risk in three genetic models. However, after excluding two study for its heterogeneity, a significantly increased risk was found in all comparisons (for C vs T: OR=1.14, 95% CI=1.03-1.27, I (2)=0, P heterpgeneity=0.420, P b=0.012; for TC vs TT: OR=1.15, 95% CI=1.01-1.30, I (2)=3.8%, P heterpgeneity=0.392, P b=0.030; for CC+TC vs TT: OR=1.16, 95% CI=1.03-1.31, I (2)=3.7%, P heterpgeneity=0.393, P b=0.015). No publication bias was found in the present study. This meta-analysis suggests that the C allele of the CAPN10 rs2975760 polymorphism is associated with an increased T2DM risk. Further large and well-designed studies are needed to confi rm this association.