Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape)

AIM: To test the hypothesis that a 'basal plus' regimenadding once-daily main-meal fast-acting insulin to basal insulin once dailywould be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction. METHODS: This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms. RESULTS: For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02). CONCLUSION: In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Mortality trends among people with type 1 and type 2 diabetes in Australia: 1997-2010

OBJECTIVE: With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current coding methods. RESEARCH DESIGN AND METHODS: A total of 1,136,617 Australians with diabetes registered on the National Diabetes Services Scheme between 1997 and 2010 were linked to the National Death Index. Excess mortality relative to the Australian population was reported as standardized mortality ratios (SMRs). Potential misclassification of CVD mortality was determined by coding CVD according to underlying cause of death (COD) and then after consideration of both the underlying and other causes listed in part I of the death certificate. RESULTS: For type 1 diabetes, the SMR decreased in males from 4.20 in 1997 to 3.08 in 2010 (Ptrend < 0.001) and from 3.92 to 3.46 in females (Ptrend < 0.01). For type 2 diabetes, the SMR decreased in males from 1.40 to 1.21 (Ptrend < 0.001) and from 1.56 to 1.22 in females (Ptrend < 0.001). CVD deaths decreased from 35.6 to 31.2% and from 31.5 to 27.2% in males and females with type 1 diabetes, respectively (Ptrend < 0.001 for both sexes). For type 2 diabetes, CVD decreased from 44.5 to 29.2% in males and from 45.5 to 31.6% in females (Ptrend < 0.001 for both sexes). Using traditional coding methods, ∼38 and 26% of CVD deaths are underestimated in type 1 diabetes and type 2 diabetes, respectively. CONCLUSIONS: All-cause and CVD mortality has decreased in diabetes. However, the total CVD mortality burden is underestimated when only underlying COD is considered. This has important ramifications for understanding mortality patterns in diabetes.

Age-specific trends from 2000-2011 in all-cause and cause-specific mortality in type 1 and type 2 diabetes: a cohort study of more than one million people

OBJECTIVE: To analyze changes by age-group in all-cause and cause-specific mortality rates from 2000-2011 in people with diabetes. RESEARCH DESIGN AND METHODS: A total of 1,189,079 (7.3% with type 1 diabetes) Australians with diabetes registered on the National Diabetes Service Scheme between 2000 and 2011 were linked to the National Death Index. Mortality rates in the total population were age standardized to the 2001 Australian population. Mortality rates were calculated for the following age-groups: 0 to <40 years, ≥ 40 to <60 years, and ≥60 to ≤85 years. Annual mortality rates were fitted using a Poisson regression model including calendar year as a covariate and age and sex where appropriate, with Ptrend reported. RESULTS: For type 1 diabetes, all-cause, cardiovascular disease (CVD), and diabetes age-standardized mortality rates (ASMRs) decreased each year by 0.61, 0.35, and 0.14 per 1,000 person-years (PY), respectively, between 2000 and 2011, Ptrend < 0.05, while cancer mortality remained unchanged. By age, significant decreases in all-cause, CVD, and diabetes mortality rates were observed in all age-groups, excluding diabetes mortality in age-group 0-40 years. For type 2 diabetes, all-cause, CVD, and diabetes ASMRs decreased per year by 0.18, 0.15, and 0.03 per 1,000 PY, respectively, Ptrend < 0.001, while cancer remained unchanged. By age, these decreases were observed in all age-groups, excluding 0-40 years, where significant increases in all-cause and cancer mortality were noted and no change was seen for CVD and diabetes mortality. CONCLUSIONS: All-cause, CVD, and diabetes ASMRs in type 1 and type 2 diabetes decreased between 2000 and 2011, while cancer ASMRs remained unchanged. However, younger populations are not benefiting from the same improvements as older populations. In addition, the absence of a decline in cancer mortality warrants urgent attention.

Tanis: a link between type 2 diabetes and inflammation?

Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001–0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.

Elevated hypothalamic beacon gene expression in Psammomys obesus prone to develop obesity and type 2 diabetes

Objective: To investigate hypothalamic beacon gene expression at various developmental stages in genetically selected diabetes-resistant and diabetes-prone Psammomys obesus. In addition, effects of dietary energy composition on beacon gene expression were investigated in diabetes-prone P. obesus. Methods: Hypothalamic beacon gene expression was measured using TaqmanÔ fluorogenic PCR in 4-, 8- and 16-week-old animals from each genetically selected line. Results: Expression of beacon was elevated in the diabetes-prone compared with diabetes-resistant P. obesus at 4 weeks of age despite no difference in body weight between the groups. At 8 weeks of age, hypothalamic beacon gene expression was elevated in diabetes-prone animals fed a high-energy diet, and was correlated with serum insulin concentration. Conclusion: P. obesus with a genetic predisposition for the development of obesity and type 2 diabetes have elevated hypothalamic beacon gene expression at an early age. Overexpression of beacon may contribute to the development of obesity and insulin resistance in these animals.

Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?

The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program (RT+WLoss) could maintain bone mineral density (BMD) and lean mass compared to moderate weight loss (WLoss) alone in older overweight adults with type 2 diabetes. We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program. This was a 12-month trial in which 36 sedentary, overweight adults aged 60 to 80 years with type 2 diabetes were randomized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months (phase 1). Thereafter, all participants completed an additional 6-month home-based training without further dietary modification (phase 2). Total body and regional BMD and bone mineral content (BMC), fat mass (FM) and lean mass (LM) were assessed by DXA every 6 months. Diet, muscle strength (1-RM) and serum total testosterone, estradiol, SHBG, insulin and IGF-1 were measured every 3 months. No between group differences were detected for changes in any of the hormonal parameters at any measurement point. In phase 1, after 6 months of gymnasium-based training, weight and FM decreased similarly in both groups (P<0.01), but LM tended to increase in the RT+WLoss (n=16) relative to the WLoss (n=13) group [net difference (95% CI), 1.8% (0.2, 3.5), P<0.05]. Total body BMD and BMC remained unchanged in the RT+WLoss group, but decreased by 0.9 and 1.5%, respectively, in the WLoss group (interaction, P<0.05). Similar, though non-significant, changes were detected at the femoral neck and lumbar spine (L2-L4). In phase 2, after a further 6 months of home-based training, weight and FM increased significantly in both the RT+WLoss (n=14) and WLoss (n=12) group, but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months. These results indicate that in older, overweight adults with type 2 diabetes, dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health.

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

Aims/hypothesis This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes.
Methods We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions.
Results We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic–euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects.
Conclusions/interpretation Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

Decreased expression of adipogenic genes in obese subjects with type 2 diabetes

Objective: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance.

Research Methods and Procedures: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [ CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARitalic gamma coactivator 1alpha, PPARitalic gamma coactivator 1beta, and PPARdelta] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity.

Results: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 plusminus 1.9 vs. 7.5 plusminus 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 plusminus 0.26 vs. 0.78 plusminus 0.17 mum; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARitalic gamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07).

Discussion: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.

High-intensity resistance training improves glycemic control in older patients with type 2 diabetes

OBJECTIVE -- To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS -- Sedentary, overweight men and women with type 2 diabetes, aged 60-80 years (n = 36), were randomized to high-intensity progressive resistance training plus moderate weight loss (RT & WL group) or moderate weight loss plus a control program (WL group). Clinical and laboratory measurements were assessed at 0, 3, and 6 months.

RESULTS -- HbA._1c fell significantly more in RT & WL than WL at 3 months (0.6 ± or -] 0.7 vs. 0.07 ± 0.8%, P < 0.05) and 6 months (1.2 ±1.0 vs. 0.4 ±0.8, P < 0.05). Similar reductions in body weight (RT & WL 2.5 ±2.9 vs. WL 3.1±2.1 kg) and fat mass (RT & WL 2.4 ± 2.7 vs. WL 2.7±2.5 kg) were observed after 6 months. In contrast, lean body mass (LBM) increased in the RT & WL group (0.5 ±1.1 kg) and decreased in the WL group (0.4±1.0) after 6 months (P < 0.05). There were no between-group differences for fasting glucose, insulin, serum lipids and lipoproteins, or resting blood pressure.

CONCLUSIONS -- High-intensity progressive resistance training, in combination with moderate weight loss, was effective in improving glycemic control in older patients with type 2 diabetes. Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes.

Issues in the provision of nursing care to people undergoing cardiac surgery who also have type 2 diabetes

There has been little investigation of the issues associated with caring for patients presenting for cardiac surgery with a comorbid diagnosis of diabetes although there is some evidence that the diabetes management is suboptimal. This study aimed to identify issues that patients and cardiac specialist nurses experience with the provision of inpatient services for people undergoing cardiac surgery who also have type 2 diabetes. A qualitative interpretive design, using individual interviews with patients and nurses, provided data about some of these issues. The study found that nurses had high levels of confidence in their cardiac care but little confidence in diabetes management. Patients described concerns about their diabetes care and treatment regimens. A 'typical journey' for a person with diabetes undergoing cardiac surgery was identified. The findings support the need to build increased capacity in specialist nurses to support diabetes care as a secondary diagnosis.

Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid 1-3

Background: Dietary fatty acids may be associated with diabetes but are difficult to measure accurately.

Objective: We aimed to investigate the associations of fatty acids in plasma and diet with diabetes incidence.

Design: This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids.

Results: In plasma phospholipid, positive associations with diabetes were seen for stearic acid [OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001] and total saturated fatty acids [OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001], whereas an inverse association was seen for linoleic acid [OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001]. Dietary linoleic [OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002], palmitic [OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012], and stearic [OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030] acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls.

Conclusions: Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.

Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes

OBJECTIVE—To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training.

RESEARCH DESIGN AND METHODS—We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60–80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA_1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months.

RESULTS—Compared with the WL group, HbA_1c decreased significantly more in the RT&WL group (–0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&WL group compared with the WL group (0.9 kg, P < 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months (P < 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months.

CONCLUSIONS—In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.

Family average income and diagnosed Type 2 diabetes in urban and rural residents in regional mainland China.

Aims: To explore the relationship between family average income (FAI; an index of socio-economic status) and Type 2 diabetes in a region of mainland China. Methods: Population-based cross-sectional study, conducted between October 2000 and March 2001 in administrative villages (n = 45) randomly selected from three urban districts and two rural counties of NanJing municipality, mainland China, with a regional population of 5.6 million. Participants were all local residents aged ≥ 35 years old (n = 29 340); 67.7% from urban areas, 32.3% from rural areas, 49.8% male and 50.2% female. Results: The response rate of eligible participants was 90.1%. The overall prevalence of self-reported Type 2 diabetes was 1.9%. After adjustment for possible confounding variables (age, gender, area of residence, body mass index, educational level, smoking status, occupational and leisure-time physical activity), participants in the higher and middle FAI categories were more than twice as likely to have Type 2 diabetes as those in the lower FAI category. Conclusions: The prevalence of Type 2 diabetes is positively related to socio-economic status (indexed by FAI) in Chinese at the population level. After controlling for potential confounding factors, people in higher socio-economic status groups are more likely to have Type 2 diabetes. These associations are consistent with other effects of epidemiological transition and identify a need for preventive initiatives.