Trajectories of HbA1c Levels in Children and Youth with Type 1 Diabetes

Purpose

To illustrate the distribution of Hemoglobin A1c (HbA1c) levels according to age and gender among children, adolescents and youth with type 1 diabetes (T1DM).

Methods

Consecutive HbA1c measurements of 349 patients, aged 2 to 30 years with T1DM were obtained from 1995 through 2010. Measurement from patients diagnosed with celiac disease (n = 20), eating disorders (n = 41) and hemoglobinopathy (n = 1) were excluded. The study sample comprised 4815 measurements of HbA1c from 287 patients. Regression percentiles of HbA1c were calculated as a function of age and gender by the quantile regression method using the SAS procedure QUANTREG.

Results

Crude percentiles of HbA1c as a function of age and gender, and the modeled curves produced using quantile regression showed good concordance. The curves show a decline in HbA1c levels from age 2 to 4 years at each percentile. Thereafter, there is a gradual increase during the prepubertal years with a peak at ages 12 to 14 years. HbA1c levels subsequently decline to the lowest values in the third decade. Curves of females and males followed closely, with females having HbA1c levels about 0.1% (1.1 mmol/mol) higher in the 25^th 50^th and 75^th percentiles.

Conclusion

We constructed age-specific distribution curves for HbA1c levels for patients with T1DM. These percentiles may be used to demonstrate the individual patient''s measurements longitudinally compared with age-matched patients.     

Recent HbA1c Values and Mortality Risk in Type 2 Diabetes. Population-Based Case-Control Study

This study aimed to evaluate mortality within 365 days of HbA1c values of <6.5% or >9.0% in participants with clinical type 2 diabetes mellitus. A matched nested case-control study was implemented, within a cohort of participants with type 2 diabetes from 2000 to 2008. Conditional logistic regression was used to model the odds ratio for mortality adjusting for comorbidity and drug utilisation. There were 97,450 participants with type 2 diabetes; 16,585 cases that died during follow up were matched to 16,585 controls. The most recent HbA1c value was <6.5% (48 mmol/mol) for 22.2% of cases and 24.2% of controls, the HbA1c was >9.0% for 9.0% of cases and 7.7% of controls. In a complete case analysis, the adjusted odds ratio (AOR) for mortality associated with most recent HbA1c <6.5% was 1.31 (95% confidence interval (CI): 1.21,1.42). After multiple imputation of missing HbA1c values the AOR was 1.20 (CI: 1.12,1.28). The complete case analysis gave an AOR for HbA1c >9.0% of 1.51 (CI: 1.33, 1.70), in the multiple imputation analysis this was 1.29 (1.17,1.41). The risk associated with HbA1c <6.5% was age dependent. In the multiple imputation analysis the AOR was 1.53 (CI: 0.84 to 2.79) at age<55 years but 1.04 (CI: 0.92, 1.17) at age 85 years and over. In non-randomised data, values of HbA1c that are either <6.5% or >9.0% may be associated with increased mortality within one year in clinical type 2 diabetes. Relative risks may be higher at younger ages.     

Development and Validation of a Novel Tool to Predict Hospital Readmission Risk Among Patients with Diabetes

Objective: To develop and validate a tool to predict the risk of all-cause readmission within 30 days (30-d readmission) among hospitalized patients with diabetes.Methods: A cohort of 44,203 discharges was retrospectively selected from the electronic records of adult patients with diabetes hospitalized at an urban academic medical center. Discharges of 60% of the patients (n = 26,402) were randomly selected as a training sample to develop the index. The remaining 40% (n = 17,801) were selected as a validation sample. Multivariable logistic regression with generalized estimating equations was used to develop the Diabetes Early Readmission Risk Indicator (DERRI™).Results: Ten statistically significant predictors were identified: employment status; living within 5 miles of the hospital; preadmission insulin use; burden of macrovascular diabetes complications; admission serum hematocrit, creatinine, and sodium; having a hospital discharge within 90 days before admission; most recent discharge status up to 1 year before admission; and a diagnosis of anemia. Discrimination of the model was acceptable (C statistic 0.70), and calibration was good. Characteristics of the validation and training samples were similar. Performance of the DERRI™ in the validation sample was essentially unchanged (C statistic 0.69). Mean predicted 30-d readmission risks were also similar between the training and validation samples (39.3% and 38.7% in the highest quintiles).Conclusion: The DERRI™ was found to be a valid tool to predict all-cause 30-d readmission risk of individual patients with diabetes. The identification of high-risk patients may encourage the use of interventions targeting those at greatest risk, potentially leading to better outcomes and lower healthcare costs.Abbreviations:DERRI™ = Diabetes Early Readmission Risk IndicatorICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical ModificationGEE = generalized estimating equationsROC = receiver operating characteristic     

C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus

In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.     

Incidence of Type 2 Diabetes in Pre-Diabetic Japanese Individuals Categorized by HbA1c Levels: A Historical Cohort Study

Objective

Reported incidence of type 2 diabetes estimated at the pre-diabetic stage differs widely (2.3–18.1% per year). Because clinicians need to know the risk of incident diabetes after a diagnosis of pre-diabetes, our objective was to estimate precise incidence of diabetes using baseline HbA_1c levels.

Methods

A historical cohort study using electronic medical record data obtained between January 2008 and December 2013. A total of 52,781 individuals with HbA_1c < 6.5% were assigned to one of six groups categorized by baseline HbA_1c level: ≤ 5.5% (n=34,616), 5.6–5.7% (n=9,388), 5.8–5.9% (n=4,664), 6.0–6.1% (n= 2,338), 6.2–6.3% (n=1,257), and 6.4% (n=518). Participants were tracked until a subsequent diagnosis of diabetes or end of follow-up during a period of 5 years.

Results

During the follow-up period (mean 3.7 years), 4,369 participants developed diabetes. The incidence of diabetes in the first year was 0.7, 1.5, 2.9, 9.2, 30.4, and 44.0% in the six HbA_1c groups, respectively. At five years the incidence was 3.6, 8.9, 13.8, 27.5, 51.6, and 67.8%, respectively (p < 0.0001 comparing the HbA_1c ≤5.5% group to the other groups). After adjustment for confounding factors, the hazard ratios compared with the HbA_1c ≤5.5% group were significantly elevated: 2.3 (95%CI 2.0–2.5), 3.4 (95%CI 2.9–3.7), 8.8 (95%CI 8.0–10.1), 26.3 (95%CI 23.3–30.1), and 48.7 (95%CI 40.8–58.1) in the five HbA_1c groups (p < 0.0001).

Conclusion

By fractionating baseline HbA_1c levels into narrower HbA_1c range groups, accuracy of estimating the incidence of type 2 diabetes in subsequent years was increased. The risk of developing diabetes increased with increasing HbA_1c levels, especially with the HbA_1c level ≥ 6.2% in the first follow-up year.     

Body Fat and Fat‐Free Mass and All‐Cause Mortality

Objective: To investigate whether the association between BMI and all‐cause mortality could be disentangled into opposite effects of body fat and fat‐free mass (FFM). Research Methods and Procedures: All‐cause mortality was studied in the Danish follow‐up study “Diet, Cancer and Health” with 27, 178 men and 29, 875 women 50 to 64 years old recruited from 1993 to 1997. By the end of year 2001, the median follow‐up was 5.8 years, and 1851 had died. Body composition was assessed by bioelectrical impedance. Cox regression models were used to estimate the relationships among body fat mass index (body fat mass divided by height squared), FFM index (FFM divided by height squared), and mortality. All analyses were adjusted for smoking habits. Results: Men and women showed similar associations. J‐shaped associations were found between body fat mass index and mortality adjusted for FFM and smoking. The mortality rate ratios in the upper part of body fat mass were 1.12 per kg/m² (95% confidence interval: 1.07, 1.18) in men and 1.06 per kg/m² (95% confidence interval: 1.02, 1.10) in women. Reversed J‐shaped associations were found between FFM index and mortality with a tendency to level off for high values of FFM. Discussion: Our findings suggest that BMI represents joint but opposite associations of body fat and FFM with mortality. Both high body fat and low FFM are independent predictors of all‐cause mortality.     

Knowledge of A1c Predicts Diabetes Self-Management and A1c Level among Chinese Patients with Type 2 Diabetes

This study was to identify current A1c understanding status among Chinese patients with type 2 diabetes, assess if knowledge of A1c affects their diabetes self-management and their glycemic control and recognize the factors influencing knowledge of A1c among patients with type 2 diabetes. A multi-center, cross-sectional survey was conducted between April and July 2010 in 50 medical centers in the Mainland China. Participants were recruited from inpatients and outpatients who were admitted to or visited those medical centers. The survey included core questions about their demographic characteristics, diabetes self-management behavior, and A1c knowledge. Overall, of 5957 patients, the percentage of patients with good understanding was 25.3%. In the multivariable logistic regression model, the variables related to the knowledge of A1c status are presented. We discovered that patients with longer diabetes duration (OR = 1.05; 95%CI = 1.04–1.06) and having received diabetes education (OR = 1.80; 95%CI = 1.49–2.17) were overrepresented in the good understanding of A1c group. In addition, compared to no education level, higher education level was statistically associated with good understanding of A1c (P<0.001). The percentage of patients with good understanding varied from region to region (P<0.001), with Eastern being highest (OR = 1.54; 95%CI = 1.32–1.80), followed by Central (OR = 1.25; 95%CI = 1.02–1.53), when referring to Western. Only a minority of patients with type 2 diabetes in China understood their A1c value. The patients who had a good understanding of their A1c demonstrated significantly better diabetes self-management behavior and had lower A1c levels than those who did not.     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

Independent Association of HbA1c and Incident Cardiovascular Disease in People Without Diabetes

Recent studies have reported no association between elevated glycated hemoglobin (HbA_1c) and incident cardiovascular disease (CVD) among women without diabetes. This study describes associations between HbA_1c and new onset CVD in a representative adult population cohort. Assessment of participants in The North West Adelaide Health Study (NWAHS), a population study of randomly selected adults (age ≥18 years, n = 4,060), included measurement of height, weight, blood pressure, fasting lipids, glucose, and HbA_1c. A self‐completed questionnaire assessed doctor‐diagnosed diabetes, CVD and stroke, smoking status, and demographics. The cohort was followed for an average 3.5 years. Of the 2,913 adults free of diabetes at baseline and follow‐up, 94 (3.5%) reported new onset coronary heart disease (CHD) and/or stroke. Compared with those with an HbA_1c ≤5.0%, risk of new onset CVD was increased in those with HbA_1c 5.4–5.6% (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4, 4.6), and ≥5.7% (OR 1.9, 95% CI 1.1, 3.4), after adjustment for other risk factors. The association was stronger in women than men (P = 0.03), and attenuated to only a small degree by addition of impaired fasting glucose (IFG), hypertension, hypercholesterolemia, BMI, waist circumference, or smoking to the model. Elevated HbA_1c is related to new onset CVD over a relatively short follow‐up period in both men and women without diabetes and who do not develop diabetes, after adjustment for other major risk factors. Unlike previous studies, this relationship was not substantially attenuated by other traditional risk factors.     

Temporality of Post‐mortem Divination and Divination of Post‐mortem Temporality1

When an Ambonwari person dies divination may be used to consult spirits as to the cause of death. Listening to the tapping of a bamboo pole—where the rhythm reflects totemic signals usually beaten on a slit‐drum—a diviner examines the links between people's wrong doings and other past deeds and events. The aim of post‐mortem divination is to reconstitute and rearrange the relationships between village clans, between clans and their land, between clans and their spirits, both of the dead and of the bush. The aim of divination is to place the events, deeds, relationships, historicity and temporality in good order again, to avoid chaotic unpredictability and the possibility of collective misfortune or even destruction. Though to a lesser degree than in initiation rituals, divination, by reordering and realigning social relationships, reconstructs society at its base. As with initiation, the aim of divination is to reconstruct time.     

Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study

Background

Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes.

Methods

Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD.

Results

A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years) than those with HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62–2.44; HR: 4.42, 95% CI: 3.80–5.14, respectively) compared with those with HbA1c of 6.0%–6.9%.

Conclusions

Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy.     

Dietary Fiber Intake Is Associated with HbA1c Level among Prevalent Patients with Type 2 Diabetes in Pudong New Area of Shanghai,China

Background

Dietary factors play an important role in glycemic control in diabetic patients. However, little is known about their effects among Chinese diabetic patients, whose diets are typically abundant in fiber and high in glycemic index (GI) values.

Methodology/Principal Findings

934 patients with type 2 diabetes and 918 healthy volunteers from Pudong New Area, Shanghai, China, were interviewed during the period of Oct-Dec, 2006 to elicit demographic characteristics and lifestyle factors. Dietary habits were assessed using a validated food frequency questionnaire. Anthropometric measurements, bio-specimen collection and biochemical assays were conducted at the interview according to a standard protocol. In this population, diabetic patients consumed lower levels of energy and macronutrients but had higher levels of fasting plasma glucose (FPG), glycolated hemoglobin A1c (HbA1c), triglyceride and body mass index than healthy adults. While the average consumption levels of the nutrients among diabetic patients did not vary along duration of the disease, the average levels of FPG and HbA1c increased with increasing duration. Regardless of diabetes duration, HbA1c level was observed lower in patients having a higher fiber or lower GI intake. Compared with those with the lowest tertile intake of fiber, the adjusted odds ratios (ORs) for poor glycemic control reduced from 0.75 (95%CI: 0.54–1.06) to 0.51 (95%CI: 0.34–0.75) with increasing tertile intake (P for trend <0.001).

Conclusions

Dietary fiber may play an important role in reducing HbA1c level. Increasing fiber intake may be an effective approach to improve glycemic control among Chinese diabetic patients.     

Relationships between Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes Mellitus

Introduction

Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects.

Methods

49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects.

Results

Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R² = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R² = 0.29, p<0.001) and metabolic flexibility (R² = 0.40, p<0.001).

Conclusions

These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin.     

Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men

We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes.