Association between glycaemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study

Aim

To investigate the association between a new composite metric, glycaemia risk index (GRI), and incident diabetic retinopathy (DR).

Methods

A total of 1204 adults with type 2 diabetes without DR at baseline were included between 2005 and 2019 from a single centre in Shanghai, China. GRI was obtained from continuous glucose monitoring data at baseline. Cox proportion hazard regression analysis was used to assess the association between GRI and the risk of incident DR.

Results

During a median follow-up of 8.4 years, 301 patients developed DR. The multivariable-adjusted hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15 ~ 28, 29 ~ 47 and > 47) were 1.00, 1.05 (95% CI 0.74-1.48), 1.33 (95% confidence interval [CI] 0.96-1.84) and 1.53 (95% CI 1.11-2.11), respectively. For each 1-SD increase in GRI, the risk of DR was increased by 20% (HR 1.20, 95% CI 1.07-1.33) after adjustment for confounders.

Conclusions

In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR. GRI has the potential to be a valuable clinical measure, which needs to be further explored in future studies.     

Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis

Aim:  Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue.
Methods:  Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov , 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed.
Results:  Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (−0.13; −0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m²; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01].
Conclusions:  The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.     

Revisiting the efficacy of long-acting insulin analogues on adults with type 1 diabetes using mixed-treatment comparisons

Aim

To perform a network meta-analysis between long-acting insulin analogues (glargine and detemir) and Neutral Protamine Hagedorn (NPH) insulin on adults with type 1 diabetes.

Methods

A systematic review of the literature was conducted according to the Cochrane Collaboration guidelines. The search for randomized controlled trials was performed in process databases, conferences and “gray literature” by 1995.

Results

We found 1051 citations comparing glargine or detemir with human insulin and 187 comparing long-acting insulin analogues. Data on Glycated Hemoglobin (HbA1c), hypoglycemia episodes, nocturnal hypoglycemia and withdrawal were meta-analyzed. After review, 8 studies comparing glargine and 9 comparing detemir with NPH and 2 comparing glargine with detemir were considered relevant. Were included 1508 patients that received glargine, 2698 detemir and 2654 NPH insulin. Efficacy data showed no significant differences in HbA1c change between glargine or detemir (once daily) and NPH insulin. Twice-daily regimen of detemir caused a difference in HbA1c that favored detemir (−0.14% [95% CI −0.21 to −0.08]). Direct comparisons showed no significant differences between glargine and detemir in safety or HbA1c mean change.

Conclusion

The long-acting insulin analogues offer little to no clinical advantages over NPH insulin, and there is no significant difference in the efficacy and safety.     

Overweight,obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study

Aims/hypothesis

Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.

Methods

Analyses were based on incident cases of LADA (n?=?425) and type 2 diabetes (n?=?1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.

Results

In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.

Conclusions/interpretation

Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

     

Pioglitazone does not affect the risk of kidney cancer in patients with type 2 diabetes

Objective

To investigate whether pioglitazone treatment of patients with type 2 diabetes mellitus was associated with an increased risk of kidney cancer.

Methods

The reimbursement databases of all Taiwanese patients with type 2 diabetes who received oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006, and a total of 1,093,675 patients with type 2 diabetes were followed up for kidney cancer incidence until the end of 2009. The incidences of kidney cancer among patients who had and had not received pioglitazone, as well as among subgroups of those treated with pioglitazone (sorted by time since starting pioglitazone, duration of treatment and cumulative dose) were calculated and hazard ratios (HRs) estimated by Cox regression analysis.

Results

Of the 1,093,675 patients, 58,172 (5.3%) had and 1,035,503 (94.7%) had not received pioglitazone, with incident kidney cancer developing in 208 (0.36%) and 3304 (0.32%) patients, respectively, and a respective incidence of 97.7 and 90.5 per 100,000 person-years. Pioglitazone and kidney cancer were not significantly associated in unadjusted (HR 1.04; 95% confidence interval (CI), 0.90–1.20), age-sex-adjusted (HR 1.09; 95% CI, 0.95–1.25), and fully adjusted (HR 1.09; 95% CI, 0.94–1.26) models. None of the dose-response parameters showed a significant trend of risk association, with all P-trends >0.10.

Conclusions

Pioglitazone does not affect the risk of kidney cancer.     

Physical Activity, Body Mass Index, and Diabetes Risk in Men: A Prospective Study

Objective

Physical activity has been associated with lower diabetes risk, but several prospective studies among women found that activity only slightly attenuated the diabetes risk associated with high body mass index (BMI). We investigated the independent and joint associations between vigorous activity and BMI on diabetes risk in men.

Methods

This was a prospective cohort design within the Physicians' Health Study, using Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident diabetes in 20,757 men without diabetes at baseline. Models were based on self-reported BMI and exercise frequency at baseline, first separately and then with a 6-category joint variable combining World Health Organization BMI category (normal/overweight/obese) with activity status (active/inactive) using weekly vigorous activity as the threshold.

Results

After a median follow-up of 23.1 years, there were 1836 cases of incident diabetes. Compared with active participants with normal BMIs, active but overweight and obese men had multivariable-adjusted HRs of 2.39 (95% CI, 2.11-2.71) and 6.22 (95% CI, 5.12-7.56). Inactive men with normal, overweight, or obese BMIs had multivariable-adjusted HRs of 1.41 (95% CI, 1.19-1.67), 3.14 (95% CI, 2.73-3.62), and 6.57 (95% CI, 5.25-8.21).

Conclusion

Active men with normal and overweight BMIs had lower diabetes hazards than their inactive counterparts, but no difference by weekly activity was seen in obese men. Elevated BMI is a key driver of diabetes risk, with relatively modest attenuation by activity.     

Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database

Aims/hypothesis

Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010.

Methods

We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (??80% use time) users of insulin glargine compared with equivalent human insulin users.

Results

Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87).

Conclusions/interpretation

There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.     

Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study

Aims/hypothesis

To assess the impact of impaired insulin secretion (IIS) and insulin resistance (IR) on type 2 diabetes incidence in a Japanese population.

Methods

This 4 year cohort study included 3,059 participants aged 30–69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Based on their insulinogenic index and HOMA-IR values, participants were classified by the criteria of the Japan Diabetes Society into four categories: normal; isolated IIS (i-IIS); isolated IR (i-IR); and IIS plus IR. They were followed up until March 2011. The incidence of type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations and from receiving medical treatment for diabetes.

Results

At baseline, 1,550 individuals (50.7%) were classified as normal, 900 (29.4%) i-IIS, 505 (16.5%) i-IR, and 104 (3.4%) IIS plus IR. During 10,553 person-years of follow-up, 219 individuals developed type 2 diabetes, with 126 (57.5%) having i-IIS at baseline. Relative to the normal group, the multivariable-adjusted HRs for type 2 diabetes in the i-IIS, i-IR and IIS plus IR groups were 8.27 (95% CI 5.33, 12.83), 4.90 (95% CI 2.94, 8.17) and 16.93 (95% CI 9.80, 29.25), respectively. The population-attributable fractions of type 2 diabetes onset due to i-IIS, i-IR, and IIS plus IR were 50.6% (95% CI 46.7%, 53.0%), 14.2% (95% CI 11.8%, 15.6%) and 12.9% (95% CI 12.3%, 13.2%), respectively.

Conclusions/interpretation

Compared with IR, IIS had a greater impact on the incidence of type 2 diabetes in a Japanese population.     

Associations of diabetes,prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study

Aim

To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank.

Materials and Methods

We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose–response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD.

Results

Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose–response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]).

Conclusions

Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.     

Perceived racism and incident diabetes in the Black Women’s Health Study

Aims/hypothesis

Our aim was to assess the association of perceived racism with type 2 diabetes, and the possible mediating influence of diet and BMI.

Methods

The Black Women’s Health Study, a follow-up of 59,000 African-American women, began in 1995. Over 16 years 5344 incident cases of diabetes occurred during 576,577 person-years. Cox proportional hazards models were used to estimated HRs and 95% CIs for categories of ‘everyday racism’ (interpersonal racism in daily life) and ‘lifetime racism’ (reporting ever treated unfairly due to race with respect to police, housing or work) and incident type 2 diabetes. Models were adjusted for age, questionnaire cycle, marital status, socioeconomic status, education, family history of diabetes, physical activity, alcohol use and smoking status, with and without inclusion of terms for dietary patterns and adult BMI.

Results

Compared with women in the lowest quartile of exposure, women in the highest quartile of exposure to everyday racism had a 31% increased risk of diabetes (HR 1.31; 95% CI 1.20, 1.42) and women with the highest exposure to lifetime racism had a 16% increased risk (HR 1.16; 95% CI 1.05, 1.27). Mediation analysis estimated that BMI accounted for half of the association between either the everyday or lifetime racism measure and incident diabetes.

Conclusions/interpretation

Perceived everyday and lifetime racism were associated with increased risk of type 2 diabetes in this cohort of African-American women and appear to be at least partly mediated by BMI.

     

Severe hypoglycaemia is a major predictor of incident diabetic retinopathy in Japanese patients with type 2 diabetes

AimHypoglycaemia is a common complication in diabetes patients. However, its relationship with retinopathy has not been well documented in patients with type 2 diabetes (T2D). This study aimed to investigate the associations between hypoglycaemia and the incidence and progression of diabetic retinopathy (DR).MethodsIn this longitudinal cohort study, which was part of the Japan Diabetes Complications Study (JDCS), adult patients with T2D were recruited at 59 diabetes clinics across Japan. Their history of hypoglycaemia was assessed by standardized self-reported questionnaires. Severe hypoglycaemia was defined as having at least one episode with coma requiring an outpatients visit or hospitalization. Adjusted hazard ratios (HRs) for incidence and progression of DR over 8 years of follow-up were determined.ResultsOf 1221 patients without DR, 127 (10.4%) had experienced non-severe hypoglycaemia within the previous year, whereas 10 (0.8%) reported severe hypoglycaemia episodes. During the 8-year follow-up involving 8492 person-years, 329 patients developed DR. In 410 patients with prevalent DR, the adjusted HRs for incident DR were 4.35 (95% CI: 1.98–9.56; P < 0.01) and, for progression of DR, 2.29 (95% CI: 0.45–11.78; P = 0.32) with severe hypoglycaemia.ConclusionHaving a history of severe hypoglycaemia was one of the strongest predictors of incident DR in patients with T2D, with a fourfold increased risk. Identifying patients with greater risks of DR based on their history of hypoglycaemia may help to personalize risk evaluation in patients with diabetes.     

A randomized trial of insulin aspart with intensified basal NPH insulin supplementation in people with Type 1 diabetes.

AIMS: Insulin aspart has been shown to improve post-prandial and overall glycaemic control in people with Type 1 diabetes. We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with standard basal NPH insulin. METHODS: The trial was conducted in 43 centres in seven countries. People with Type 1 diabetes were randomized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25% increase in bedtime NPH dose (n = 187), or to mealtime human unmodified insulin with once or twice daily basal NPH insulin (n = 181). Efficacy and safety were evaluated at 12 weeks (primary evaluation period) and 64 weeks. RESULTS: At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups: -0.09 (95% confidence interval (CI) -0.23, +0.05)% and -0.14 (-0.32, +0.04)%. Post-prandial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28% smaller with insulin aspart (35.2 +/- 3.2 vs. 48.9 +/- 3.1 mmol/l h, P = 0.0015). No significant differences were found in mild or severe hypoglycaemia, or adverse event rate. At 64 weeks treatment satisfaction was higher in the insulin aspart group (difference 1.57 (95% CI 0.49, 2.64) points, P = 0.004), while quality of life was not different. CONCLUSIONS: Improved post-prandial glycaemic control and treatment satisfaction with insulin aspart were confirmed. Intensifying basal insulin supplementation resulted in a similar HbA1c decrement as previously found with the use of insulin aspart and standard NPH insulin supplementation. This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice.     

Insulin analogues in children with Type 1 diabetes: a 52‐week randomized clinical trial

Aims

This 52‐week, randomized, multinational, open‐label, parallel‐group, non‐inferiority trial investigated the efficacy and safety of basal–bolus treatment with insulin detemir vs. NPH (neutral protamine Hagedorn) insulin, in combination with insulin aspart, in subjects aged 2–16 years with Type 1 diabetes mellitus.

Methods

Of the 347 randomized and exposed subjects, 177 received insulin detemir and 170 NPH insulin, both administered once or twice daily in combination with mealtime insulin aspart. Glycaemic measurements and weight were followed over 52 weeks.

Results

After 52 weeks, insulin detemir was shown to be non‐inferior to NPH insulin with regard to HbA_1c [mean difference insulin detemir–NPH: 1.30 mmol/mol, 95% CI –1.32 to 3.92 (0.12%, 95% CI –0.12 to 0.36) in the full analysis set and 1.41 mmol/mol, 95% CI –1.26 to 4.08 (0.13%, 95% CI –0.12 to 0.37) in the per protocol analysis set]. Hypoglycaemic events per subject‐year of exposure of 24‐h and nocturnal hypoglycaemia were significantly lower with insulin detemir than with NPH insulin (rate ratio 0.76, 95% CI 0.60–0.97, P = 0.028 and 0.62, 95% CI 0.47–0.84, P = 0.002, respectively). Weight standard deviation (sd ) scores (body weight standardized by age and gender) decreased with insulin detemir, but increased slightly with NPH insulin (change: –0.12 vs. 0.04, P < 0.001). At end of the trial, median insulin doses were similar in both treatment groups.

Conclusions

Insulin detemir was non‐inferior to NPH insulin after 52 weeks' treatment of children and adolescents aged 2–16 years, and was associated with a significantly lower risk of hypoglycaemia, together with significantly lower weight sd score when compared with NPH insulin.     

The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study

Aims/hypothesis

Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.

Methods

A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.

Results

A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.

Conclusions/interpretation

Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.     

Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Aims

Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes-related characteristics are independently associated with fracture risk. In this post-hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility.

Materials and Methods

The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co-micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex-specific diabetes-related parameters independently associated with incident fractures.

Results

Over 49,470 person-years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person-years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL-cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04).

Conclusions

Insulin use and sex-specific complications (in men, macrovascular disease; in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.     

Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women

Aims/hypothesis

Coffee and tea consumption has been associated with a lower type 2 diabetes risk but little is known about how changes in coffee and tea consumption influence subsequent type 2 diabetes risk. We examined the associations between 4 year changes in coffee and tea consumption and risk of type 2 diabetes in the subsequent 4 years.

Methods

We prospectively followed 48,464 women in the Nurses’ Health Study (NHS; 1986–2006), 47,510 women in NHS II (1991–2007) and 27,759 men in the Health Professionals Follow-up Study (HPFS; 1986–2006). Diet was assessed every 4 years using a validated food-frequency questionnaire. Self-reported cases of incident type 2 diabetes were validated by supplementary questionnaires.

Results

During 1,663,319 person-years of follow-up, we documented 7,269 cases of incident type 2 diabetes. Participants who increased their coffee consumption by more than 1 cup/day (median change?=?1.69 cups/day) over a 4 year period had an 11% (95% CI 3%, 18%) lower risk of type 2 diabetes in the subsequent 4 years compared with those who made no changes in consumption. Participants who decreased their coffee intake by more than 1 cup/day (median change?=??2 cups/day) had a 17% (95% CI 8%, 26%) higher risk for type 2 diabetes. Changes in tea consumption were not associated with type 2 diabetes risk.

Conclusions/interpretation

Our data provide novel evidence that increasing coffee consumption over a 4 year period is associated with a lower risk of type 2 diabetes, while decreasing coffee consumption is associated with a higher risk of type 2 diabetes in subsequent years.     

Impact of low-density lipoprotein cholesterol on cardiovascular outcomes in people with type 2 diabetes: A meta-analysis of prospective cohort studies

Aims

To estimate the prospective association of low-density lipoprotein (LDL) cholesterol on cardiovascular disease (CVD) risk among people with type 2 diabetes.

Methods

We used extensive literature searching strategies to locate prospective cohort studies that reported LDL cholesterol levels as a risk factor for cardiovascular events. We conducted meta-analytic procedures for two outcomes: incident CVD and CVD mortality.

Results

A total of 16 studies were included in this analysis with a mean follow-up range of 4.8–11 years. The pooled relative risk associated with a 1 mmol/L increase in LDL cholesterol in people with type 2 diabetes was 1.30 (95% confidence interval [CI], 1.19–1.43) for incident CVD, and 1.50 (95% CI, 1.25–1.80) for CVD mortality, respectively. Subgroup analyses showed that for incident CVD, the pooled relative risk was 1.28 (95% CI, 1.17–1.41) for 7 studies adjusted for blood pressure and/or glucose concentration (or insulin concentration, glycated hemoglobin) and 1.40 (95% CI, 1.05–1.86) for 3 studies that did not adjust for these variables.

Conclusions

Our study demonstrates that LDL cholesterol was associated with an increased risk for cardiovascular outcomes in people with type 2 diabetes, independent of other conventional risk factor.     

Risk of Recurrent Venous Thromboembolism: A Danish Nationwide Cohort Study

Purpose

In this study, we aimed to estimate recurrence risk after incident venous thromboembolism, stratified according to unprovoked, provoked, and cancer-related venous thromboembolism in a prospective cohort of inpatients and outpatients receiving routine care.

Calcium and phosphate concentrations and future development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study

Aims/hypothesis

Low phosphate and high calcium concentrations have been linked to altered glucose tolerance and reduced insulin sensitivity in non-diabetic individuals. The aim of this study was to examine the relationships of calcium and phosphate levels and the calcium–phosphate product with the development of type 2 diabetes.

Methods

Participants were 863 African-Americans, Hispanics and non-Hispanic whites in the Insulin Resistance Atherosclerosis Study who were free of diabetes at baseline. The mean follow-up period was 5.2 years. The insulin sensitivity index (S_I) and acute insulin response (AIR) were directly measured using the frequently sampled IVGTT.

Results

Calcium concentration (OR per 1 SD unit increase, 1.26 [95% CI 1.04, 1.53]) and calcium–phosphate product (OR 1.29 [95% CI 1.04, 1.59]) were associated with incident diabetes after adjustment for demographic variables, family history of diabetes, and 2 h glucose. The relationship between phosphate concentration and progression to diabetes was close to statistical significance (OR 1.21 [95% CI 0.98, 1.49]). Calcium concentration (OR 1.37 [95% CI 1.09, 1.72]) and calcium–phosphate product (OR 1.39 [95% CI 1.09, 1.77]) remained associated with incident diabetes after additional adjustment for BMI, plasma glucose, S_I, AIR, C-reactive protein, estimated GFR, diuretic drugs and total calcium intake.

Conclusions/interpretation

Elevated serum calcium and calcium–phosphate product are associated with increased risk of developing type 2 diabetes independently of measured glucose, insulin secretion and insulin resistance. Future studies need to analyse the role of calcium–phosphate homeostasis in the pathophysiology of diabetes.     

Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Severe Hypoglycemia

Purpose

The magnitude of the risk of severe hypoglycemia associated with sulfonylureas as the initial treatment for type 2 diabetes in the real-world setting is unknown. We assessed the risk of severe hypoglycemia associated with initiating monotherapy with sulfonylurea compared with metformin for the treatment of type 2 diabetes.