Eleven-year multimorbidity burden among 637 255 people with and without type 2 diabetes: a population-based study using primary care and linked hospitalisation data.

OBJECTIVES: To compare the patterns of 18 physical and mental health comorbidities between people with recently diagnosed type 2 diabetes (T2D) and people without diabetes and how these change by age, gender and deprivation over time between 2004 and 2014. Also, to develop a metric to identify most prevalent comorbidities in people with T2D. DESIGN: Population-based cohort study. SETTING: Primary and secondary care, England, UK. PARTICIPANTS: 108 588 people with T2D and 528 667 comparators registered in 391 English general practices. Each patient with T2D aged ≥16 years between January 2004 and December 2014 registered in Clinical Practice Research Datalink GOLD practices was matched to up to five comparators without diabetes on age, gender and general practice. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of 18 physical and mental health comorbidities in people with T2D and comparators categorised by age, gender and deprivation. Odds for association between T2D diagnosis and comorbidities versus comparators. A metric for comorbidities with prevalence of ≥5% and/or odds ≥2 in patients with T2D. RESULTS: Overall, 77% of patients with T2D had ≥1 comorbidity and all comorbidities were more prevalent in patients with T2D than in comparators. Across both groups, prevalence rates were higher in older people, women and those most socially deprived. Conditional logistic regression models fitted to estimate (OR, 95% CI) for association between T2D diagnosis and comorbidities showed that T2D diagnosis was significantly associated with higher odds for all conditions including myocardial infarction (OR 2.13, 95% CI 1.85 to 2.46); heart failure (OR 2.12, 1.84 to 2.43); depression (OR 1.75, 1.62 to 1.89), but non-significant for cancer (OR 1.12, 0.98 to 1.28). In addition to cardiovascular disease, the metric identified osteoarthritis, hypothyroidism, anxiety, schizophrenia and respiratory conditions as highly prevalent comorbidities in people with T2D. CONCLUSIONS: T2D diagnosis is associated with higher likelihood of experiencing other physical and mental illnesses. People with T2D are twice as likely to have cardiovascular disease as the general population. The findings highlight highly prevalent and under-reported comorbidities in people with T2D. These findings can inform future research and clinical guidelines and can have important implications on healthcare resource allocation and highlight the need for more holistic clinical care for people with recently diagnosed T2D.

Male hypogonadism: 14-year prospective outcome in 550 men with type 2 diabetes.

INTRODUCTION: Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%-40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14-year follow-up study to evaluate the influence of baseline testosterone level on T2DM outcomes. RESEARCH DESIGN AND METHODS: A total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone-binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow-up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system. RESULTS: Mean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (<10 nmol/L) was 7.6 ± 2.0 nmol/L (n = 154) and 142 men had a free testosterone <190 pmol/L. During the 14-year duration follow-up, 22% of men experienced a myocardial infarction, 18% experienced a stroke, 11% developed angina, 14% underwent coronary revascularization. About 38% of the men initially recruited died. A lower total testosterone was associated with a higher body mass index (kg/m2) at follow-up: regression coefficient -0.30 (95% CI -0.445 to -0.157), P = 0.0001. The mortality rate was higher in patients with lower total testosterone compared to normal baseline total testosterone (5.0% vs 2.8% per year, P < 0.0001). A similar phenomenon was seen for dihydrotestosterone (4.3% vs 2.9% per year, P = 0.002) for normal vs low dihydrotestosterone) and for lower SHBG. Over the whole follow-up period 36.1% (143/396), men with normal baseline testosterone died vs 55.8% (86/154) of hypogonadal men at baseline. In Cox regression, the age-adjusted hazard ratio (HR) for higher mortality associated with low total testosterone was 1.54 (95% CI: 1.2-2.0, P < 0.002), corresponding to a 3.2 year reduced life expectancy for hypogonadal T2DM men. CONCLUSION: Low testosterone and dihydrotestosterone levels are associated with higher all-cause mortality in T2DM men. Hypogonadal men with T2DM should be considered as very high risk for cardiovascular events/death.

A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial.

BACKGROUND: Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided. OBJECTIVES: Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients. METHODS: Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 µmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported. RESULTS: Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein. CONCLUSIONS: High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

Atorvastatin administration is associated with dose-related changes in IGF bioavailability.

OBJECTIVE: IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins. DESIGN AND METHODS: We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (S.D.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg). RESULTS: Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: -3 (-21 to 14) ng/ml; IGF2: -23 (-65 to 18) ng/ml and IGFBP3: -0.34 (-0.71 to 0.03) µg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant -0.41 (-0.69 to 0.13, P=0.004). CONCLUSION: IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.