Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

Meal-derived glucagon responses are related to lower hepatic phosphate concentrations in obesity and type 2 diabetes.

AIM: Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. METHODS: In this observational study, lean insulin-sensitive control subjects (BMI: 23.2±1.5kg/m2), age-matched insulin-resistant obese subjects (BMI: 34.3±1.7kg/m2) and similarly obese elderly T2D patients (BMI: 32.0±2.4kg/m2) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (Pi) and lipids using 31P/1H magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. RESULTS: MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P<0.001), while glucagon concentrations were comparable across all three groups. At 260min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r=0.60) and postprandial hepatocellular lipid levels (160min: r=0.51, 240min: r=0.59), and negatively with adipose tissue insulin sensitivity (r=-0.73). Higher meal-induced glucagon release (iAUC0-260min) correlated with lower fasting (r=-0.62) and postprandial Pi levels (160min: r=-0.43, 240min: r=-0.42; all P<0.05). Higher meal-induced release of GIP (iAUC0-260min) correlated positively with fasting (r=0.54) and postprandial serum triglyceride concentrations (iAUC0-260min, r=0.54; all P<0.01). CONCLUSION: Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic Pi suggest a role for glucagon in hepatic energy metabolism.

Inverse association of insulin antibody levels with insulin sensitivity in adults with Type 1 diabetes.

AIMS: Insulin resistance may contribute to the pathogenesis of autoimmune-mediated diabetes. Antibodies against ß-cell-associated molecules, comprising islet cell antigen (ICA), glutamic acid decarboxylase (GAD) and insulin, characterize the autoimmune process. Because the link between insulin resistance and autoimmunity might be relevant for disease progression and treatment, we hypothesized that insulin resistance associates positively with ß-cell-directed antibodies in newly diagnosed Type 1 diabetes. METHODS: Within the German Diabetes Study, an observational study including adults with newly diagnosed diabetes, 142 adults [84 men, 58 women; age 33.1 (26.4, 41.9) years; diabetes duration 6.3 (4.2, 9.1) months] positive for at least one antibody against ICA, GAD or insulin underwent hyperinsulinaemic-euglycaemic clamp tests to assess insulin sensitivity (M-value) in a cross-sectional setting. RESULTS: Insulin-directed antibodies were inversely correlated with M-values (ß = -0.039). Albeit not strong, the association persisted after adjustment for age, sex and BMI, and even after further adjustment for confounders reflecting exposure to exogenous insulin and residual ß-cell secretory capacity. Correlation network-based analyses revealed a complex interaction between levels of fasting insulin and of insulin antibodies with respect to their relationship with the M-value. GAD- or ICA-directed antibodies did not correlate with insulin sensitivity. CONCLUSIONS: In adults with recent-onset Type 1 diabetes expressing at least one ß-cell-directed antibody, insulin sensitivity is inversely related to insulin antibody titres, but not to other autoantibodies. Our finding may allow for the identification of insulin resistance in adults with high levels of insulin antibodies.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes.

AIMS: To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and ß-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. METHODS: Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic ß-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. RESULTS: Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% (P = 0.035). CONCLUSIONS: Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093).

Effects of Long-Term Exercise Interventions on Glycaemic Control in Type 1 and Type 2 Diabetes: a Systematic Review.

Aim: Physical activity is one of the cornerstones in the prevention and management of diabetes mellitus, but the effects of different training forms on metabolic control still remain unclear. The aims of this review are to summarize the recommendations of 5 selected diabetes associations and to systematically review the effects of long-term supervised exercise interventions without calorie-restriction on glycemic control in people with type 1 and 2 diabetes focusing on resistance, endurance and combined training consisting of both endurance and resistance training. Methods: Literature searches were performed using MEDLINE for articles published between January 1, 2000 and March 17, 2015. Of 76 articles retrieved, 15 randomized and controlled studies met the inclusion criteria and allowed for examining the effect of exercise training in type 1 and 2 diabetes. Results: Diabetes associations recommend volume-focused exercise in their guidelines. In our analysis, all 3 training forms have the potential to improve the glycemic control, as assessed by HbA1c (absolute changes in HbA1c ranging from -0.1% to -1.1% (-1.1 to -12 mmol/mol) in resistance training, from -0.2% to -1.6% (-2.2 to -17.5 mmol/mol) in endurance training and from +0.1% to -1.5% (+1.1 to -16.4 mmol/mol) in combined training, respectively). Conclusions: There is evidence that combined exercise training may improve glycemic control to a greater extent than single forms of exercise, especially under moderate-intensive training conditions with equal training durations. In addition, intensity of training appears to be an important determinant of the degree of metabolic improvement. Nonetheless, it is still unknown to what extent exercise effects glycemic homeostasis.

The Impact of Dietary Factors on Glycemic Control, Insulin Sensitivity and Secretion in the First Years after Diagnosis of Diabetes.

BACKGROUND: Dietary factors play an important role in the prevention of diabetes mellitus. We tested the hypothesis that dietary factors related to diabetes onset also associate with its progression, i. e., early time courses of insulin sensitivity and secretion in both type 1 and type 2 diabetes. METHODS: In a prospective observational study, well-controlled recent-onset diabetes patients (n=127) underwent detailed metabolic characterization within the first year after diagnosis. A follow-up was conducted 2 years after the first examination. Insulin secretion and sensitivity were assessed by intravenous glucose tolerance testing. Baseline food consumption was analyzed by a food propensity questionnaire. Multivariate linear regression analysis was used to assess associations between consumption frequencies at baseline with metabolic changes during the first 2 years. RESULTS: Within the first 2 years, metabolic control did not change in patients with type 1 and type 2 diabetes on average. In type 1 diabetes, an increased consumption frequency of refined grains by one time/day at baseline associated with higher HbA1c by 0.60% (95% CI: 0.04; 1.16), P=0.04 after 2 years compared to baseline. In type 2 diabetes, an increased consumption frequency of meat/meat products by one time/day at baseline associated with lower beta-cell adaptation index (-7.25% (95% CI: -13.16; -0.93), P=0.03) after adjustment for age, sex, BMI, and changes of BMI and glucose-lowering medication. CONCLUSION: Dietary factors associate with the initial course of diabetes. Reduced consumption of refined grains in type 1 diabetes and of meat products in type 2 diabetes may contribute to preservation of insulin secretion and sensitivity.

Do dogs sense hypoglycaemia?

AIMS: To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it. METHODS: Electronic databases were searched for all types of articles reporting on untrained or trained 'diabetes alert' dogs. Articles published up until December 2014 in the English or German language were included. RESULTS: Several case reports and observational studies provide evidence that animals can perform at a level above that attributable to chance, and may reliably detect low diurnal as well as nocturnal hypoglycaemic episodes. Behavioural changes in untrained dogs were reported during 38-100% of hypoglycaemic events experienced by their owners. The sensitivity and specificity of the performance of trained diabetes alert dogs sensing hypoglycaemia ranged from 22 to 100% and 71 to 90%, respectively. Additionally, 75-81% of patients with diabetes who owned a trained dog reported a subsequent improvement in their quality of life. Nevertheless, the available data are limited and heterogeneous because they rely on low patient numbers and survey-based studies prone to recall bias. CONCLUSION: Further research is needed to confirm the preliminary data on the reliability and mechanism underlying the dogs' abilities to detect hypoglycaemia, and its impact on patient outcomes.