Management of lipid abnormalities in patients with diabetes

Purpose of Review: To describe lipid abnormalities in diabetes, when they occur and the evidence base for lipid management with established and new drugs to prevent diabetes complications. We also discuss how to manage statin intolerance. Recent Findings: Statins remain first-line therapy in patients with diabetes, though newer therapies to reduce LDL-C have emerged, including ezetimibe as an add-on therapy to statins, and injectable PCSK9 inhibitors, both of which are safe and effective in diabetes. Emerging evidence suggests a need to consider lipid-lowering therapies more often in younger patients with both type 1 and type 2 diabetes. Summary: Statins remain the cornerstone of lipid management in diabetes but other options are increasing. There is also now evidence for better managing apparent statin intolerance. Notably, younger patients lose the most life years from their diabetes, an observation that future guidelines need to consider

Sex differences in the association of risk factors for heart failure incidence and mortality

Background: There are known risk factors associated with the development of heart failure (HF), but it is not fully understood whether these differ by sex. Objectives: To investigate sex differences in risk factors for HF incidence and mortality. Methods: 468 941 participants (55.9% women, age range 37–73 years) were included. Established CVD risk factors (hypertension, hypercholesterolaemia, diabetes type 1 and 2, adiposity, smoking, physical activity and poor diet) and novel risk factors (grip strength, fitness, TV viewing and sleep duration) were the exposures of interest. HF incidence and mortality were the outcomes. Results: Over a mean follow-up of 9.0 years, 1812 participants developed HF and 763 died due to HF. Women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), hypertension, hypercholesterolaemia, low levels of physical activity and fitness, low strength, high levels of TV viewing, sleep duration <7 hours/day, smokers; those who were underweight and who were obese, had high body surface area and those who drink >14 units of alcohol were at higher risk of HF incidence. However, in women T2DM, hypercholesterolaemia, >3 hours/day of TV and sleep <7 hours/day, low level of physical activity and high level of TV viewing were more strongly associated with HF incidence compared with men. Conclusion: Several modifiable risk factors (in particular diabetes) appear more strongly associated with HF in women compared with men. The relevance of these findings to HF characteristics and future outcomes needs to be established

Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants

Objective: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score. Design: Prospective population based study. Setting: UK Biobank. Participants: 502 293 participants (54% women) aged 40-69 years. Main outcome measures: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate). Results: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years’ follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009). Conclusion: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility

Contribution of type 2 diabetes to all-cause mortality, cardiovascular disease incidence and cancer incidence in white Europeans and South Asians: findings from the UK Biobank population-based cohort study

Objective: To investigate whether the health implications of having type 2 diabetes (T2D) were different in South Asian compared with white European participants. Research design and methods: Prospective data from UK Biobank were used, and 457 935 participants of white European and 7102 of South Asian background were included. Cox proportional regression was performed to investigate the association between T2D and health outcome by ethnicity. Results: Over a mean of 7.0 years (IQR 6.3–7.6) of follow-up, 12 974 participants had died, and 30 347 and 27 159 developed cardiovascular disease (CVD) and cancer, respectively. South Asians had a higher risk for CVD mortality (HR: 1.42, 95% CI 1.07 to 1.89) and incidence (HR: 1.78, 95% CI 1.63 to 1.94), but a decreased risk for cancer mortality (HR: 0.59, 95% CI 0.41 to 0.85) and incidence (HR: 0.80, 95% CI 0.70 to 0.92) compared with white Europeans. Compared with individuals without T2D, both white Europeans and South Asians with T2D had a higher risk for all-cause mortality (1.59 (1.48 to 1.71) vs 2.83 (1.76 to 4.53)), CVD mortality (2.04 (1.82 to 2.28) vs 4.40 (2.37 to 8.16)) and CVD incidence (1.37 (1.31 to 1.44) vs 1.60 (1.31 to 1.95)), respectively. However, the magnitude of the risk was higher for South Asians than white Europeans. Conclusions: Although T2D was associated with a higher risk for all-cause mortality and CVD incidence and mortality, in both white Europeans and South Asians, the risk experienced by South Asians with T2D was higher than their white European counterparts

Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study

Objective: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular, respiratory, COPD and cancer mortality and incidence. Design: Prospective population based study. Setting: UK Biobank. Participants: Of the 502,628 (5.5% response rate) participants recruited by UK Biobank, we included 73,259 (14.6%) participants with available data in this analysis. Of these, 1,374 participants died and 4,210 developed circulatory diseases, 1,293 respiratory diseases and 4,281 cancer, over a median of 5.0 years [IQR 4.3–5.7] follow-up. Main outcome measures - All-cause mortality and circulatory disease, respiratory disease, chronic obstructive e pulmonary disease (COPD) and cancer (any-type, colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated with a submaximal cycle ergometer test. Results: The hazard ratio for all-cause mortality for each MET higher fitness was 0.96 ([95% CI 0.93–0.98]). Similar results were observed for incident circulatory (HR 0.96 [0.95–0.97]), respiratory disease (HR 0.96 [0.94–0.98]), COPD (HR 0.90 [0.86–0.95]), and colorectal cancer (HR 0.96 [0.92–1.00]). Nonlinear analysis revealed that a high level of fitness (>10 METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07–1.44]) and prostate cancer (HR 1.16 [1.02–1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle, and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow up. Conclusions: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of cardiovascular, respiratory disease and colorectal cancer

Association between adiposity levels and cognitive impairment in the Chilean older adult population

Although both obesity and ageing are risk factors for cognitive impairment, there is no evidence in Chile on how obesity levels are associated with cognitive function. Therefore, the aim of the present study was to investigate the association between adiposity levels and cognitive impairment in older Chilean adults. This cross-sectional study includes 1384 participants, over 60 years of age, from the Chilean National Health Survey 2009–2010. Cognitive impairment was evaluated using the Mini-Mental State Examination. BMI and waist circumference (WC) were used as measures of adiposity. Compared with people with a normal BMI, the odds of cognitive impairment were higher in participants who were underweight (OR 4·44; 95 % CI 2·43, 6·45; P < 0·0001), overweight (OR 1·86; 95 % CI 1·06, 2·66; P = 0·031) and obese (OR 2·26; 95 % CI 1·31, 3·21; P = 0·003). The associations were robust after adjustment for confounding variables. Similar results were observed for WC. Low and high levels of adiposity are associated with an increased likelihood of cognitive impairment in older adults in Chile

Association of fitness and grip-strength with heart failure: findings from the UK Biobank population-based study

Objective: To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. Patients and Methods: Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. Results: During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1–metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). Conclusion: Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Insulin sensitivity in men with impaired glucose regulation and endurance-trained athletes: the roles of skeletal muscle and adipose tissue

Abstract not currently available