Diabet. Med. 30, 46–55 (2013)
Aims Whether long‐term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long‐term ...differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group.
Methods This long‐term follow‐up (median 10 years, interquartile range 9.0–10.5) of the three‐arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1‐year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow‐up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually.
Results After 10 years’ follow‐up from Diabetes Prevention Program baseline, major reductions were seen for systolic (−2 to −3) and diastolic (−6 to −6.5 mmHg) blood pressure, and for LDL cholesterol (−0.51 to −0.6 mmol/l) and triglycerides (−0.23 to −0.25 mmol/l) in all groups, with no between‐group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study.
Conclusion Overall, intensive lifestyle intervention achieved, with less medication, a comparable long‐term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.
Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether ...the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later.
A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted.
A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD (<25 cm) and normal BMI (18.5-24.9 kg/m(2)), whereas those both obese (BMI >30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55).
Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.
Context:
Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women ...with a history of GDM.
Objective:
The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study.
Design:
This was a randomized controlled clinical trial with an observational follow-up.
Setting:
The study was conducted at 27 clinical centers.
Participants:
Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry.
Interventions:
Interventions included placebo, ILS, or metformin.
Outcomes Measure:
Outcomes measure was diabetes mellitus.
Results:
Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes.
Conclusions:
Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.
Summary
Background The association between body‐mass‐index (BMI), alcohol consumption and their joint effect in increasing the risk of elevated serum alanine (ALT) and aspartate (AST) is unclear in ...older community‐dwelling adults.
Aim To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community‐dwelling adults in the United States.
Methods A cross‐sectional, population‐based study in participants (n = 2364) from the Rancho Bernardo Study (54% women; mean age: 70 years, BMI: 25 kg/m2, alcohol users: 63%) who attended a research visit in 1984–87. BMI was recorded by a trained nurse and alcohol use ascertained by a validated questionnaire. Odds‐ratio (OR) and 95% confidence intervals (CI) of elevated serum ALT and AST (defined as ≥30 U/L in men and ≥19 U/L in women) were calculated for alcohol and BMI separately and their joint exposure using logistic regression models.
Results In multivariate logistic regression models adjusted for age, alcohol use, total cholesterol, serum triglycerides, fasting plasma glucose, systolic blood pressure, and diabetes mellitus, obesity independently increased the odds of elevated ALT in this cohort of older men and women by 3.0 (95% CI, 1.7–5.3) and 1.8 (95% CI, 1.1–2.7) respectively. Joint effects of consuming >3 alcoholic drinks/day and obesity raised the odds of elevated ALT by 8.9 (95% CI, 2.4–33.1) and AST by 21‐fold (95% CI, 2.6–170.1), demonstrating synergism. Obese participants had higher odds of elevated ALT even at 0 ≤ 1 drink/day.
Conclusions In older men and women, the combination of obesity with alcohol is synergistic in increasing the risk of liver injury.
Aim
Approximately half of the participants in the Diabetes Prevention Outcomes Study (DPPOS) had diabetes after 15 years of follow‐up, whereas nearly all the others remained with pre‐diabetes. We ...examined whether formerly unexplored factors in the DPPOS coexisted with known risk factors that posed additional risk for, or protection from, diabetes as well as microvascular disease.
Methods
Cox proportional hazard models were used to examine predictors of diabetes. Sequential modelling procedures considered known and formerly unexplored factors. We also constructed models to determine whether the same unexplored factors that associated with progression to diabetes also predicted the prevalence of microvascular disease. Hazard ratios (HR) are per standard deviation change in the variable.
Results
In models adjusted for demographics and known diabetes risk factors, two formerly unknown factors were associated with risk for both diabetes and microvascular disease: number of medications taken (HR = 1.07, 95% confidence intervals (95% CI) 1.03 to 1.12 for diabetes; odds ratio (OR) = 1.10, 95% CI 1.04 to 1.16 for microvascular disease) and variability in HbA1c (HR = 1.02, 95% CI 1.01 to 1.03 for diabetes; OR = 1.06, 95% CI 1.04 to 1.09 for microvascular disease per sd). Total comorbidities increased risk for diabetes (HR = 1.10, 95% CI 1.04 to 1.16), whereas higher systolic (OR = 1.22, 95% CI 1.13 to 1.31) and diastolic (OR = 1.14, 95% CI 1.05 to 1.22) blood pressure, as well as the use of anti‐hypertensives (OR = 1.41, 95% CI 1.23 to 1.62), increased risk of microvascular disease.
Conclusions
Several formerly unexplored factors in the DPPOS predicted additional risk for diabetes and/or microvascular disease – particularly hypertension and the use of anti‐hypertensive medications – helping to explain some of the residual disease risk in participants of the DPPOS.
What's new?
The Diabetes Prevention Outcomes Study (DPPOS) is the largest global trial to date aimed at preventing or delaying diabetes onset in a high‐risk group.
We have retained ˜ 85% of the original participants for nearly 20 years.
At the time of the most recent data lock, ˜ 50% of participants had developed diabetes, whereas the others had not. This analysis examines residual risk factors for diabetes and microvascular disease not formerly explored in the DPPOS.
Simple clinical information, such as the number of medications taken and glycaemic variability, are associated with increased risk for diabetes and microvascular disease.
Hypertension and use of anti‐hypertensive medication predicted composite microvascular disease independent of diabetes status.
Summary In women, but not men, lower 25-hydroxyvitamin D 25(OH)D levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective ...analyses. Introduction Preserved physical function may explain how 25(OH)D supplementation reduces falls and fractures. Methods A total of 1,065 community-dwelling men and women (mean age 74.6 years) with 25(OH)D levels and performance on timed up and go (TUG) and timed chair stand (TCS) were seen in 1997-1999; 769 (72%) participants returned for follow-up. Associations were examined using generalized linear models. Results 25(OH)D levels were higher in men than women, but the prevalence of vitamin D insufficiency defined as 25(OH)D <75 nmol/L was 14%. There were no baseline sex differences in TUG or TCS. However, after 2.5 years, decline in TCS and TUG was greater in women than men (11% vs. 3%; p < 0.001). Women in the lowest 25(OH)D quartile (<80 nmol/L) compared to the highest quartile had an accelerated rate of functional decline on the TUG and TCS independent of covariates. No significant associations were seen in men. Conclusion In women, but not men, lower 25(OH)D levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective analyses. These results provide additional evidence that 25(OH)D is associated with physical function, which may explain how vitamin D supplementation reduces falls and fractures.
We examined the associations of metabolic syndrome (MS) with BMD, osteoporosis, and osteoporotic fractures in 417 men and 671 women from the Rancho Bernardo Study. After adjusting for BMI, MS was ...associated with lower, not higher BMD. Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures.
The metabolic syndrome (MS) is a cluster of risk factors, including abdominal obesity, high glucose, triglycerides, hypertension and low HDL levels, associated with cardiovascular disease morbidity. The association between components of the MS and bone mineral density (BMD) has been researched, but results are contradictory.
We used multivariate regression models to examine the cross-sectional associations of MS defined by NCEP-ATP III criteria with BMD and osteoporosis, and the longitudinal association of MS with fractures in 420 men and 676 women from the Rancho Bernardo Study.
Prevalence of MS at baseline was 23.5% in men and 18.2% in women. In age-adjusted analyses, men and women with MS had higher BMD at total hip when compared to those without MS (p < 0.001 and p = 0.01, respectively). Men but not women with MS also had higher BMD at femoral neck (p = 0.05). After adjusting for BMI, these associations were reversed, such that MS was associated with lower and not higher BMD.
Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures. The association of MS with higher BMD was explained by the higher BMI in those with MS.
To investigate the association between diabetes and impaired fasting glucose (IFG) and cognition and risk of developing both dementia and mild cognitive impairment (MCI) in older women.
The authors ...analyzed data from a 4-year randomized trial of raloxifene among 7,027 osteoporotic postmenopausal women (mean age, 66.3 years) at 178 sites. Diabetes was defined by history, fasting blood glucose > or =7.0 mmol/L (> or =126 mg/dL), or use of hypoglycemic agents; IFG was defined as fasting glucose <7.0 mmol/L but >6.11 mmol/L (110 mg/dL); all others were considered to have normal glucose (NG). The main outcome was baseline and 4-year change on five standardized cognitive tests (z scores with lower scores indicating worse performance) and risk of developing clinically significant impairment (dementia, mild cognitive impairment, or very low cognitive score).
A total of 267 (3.8%) women had diabetes and 297 (4.2%) had IFG. Women with IFG had worse baseline cognitive scores compared to women with NG but better scores than diabetics (age-adjusted composite z score based on five tests: NG 0.40, 95% CI 0.30 to 0.49; IFG 0.14, 95% CI -0.36 to 0.64; diabetics -0.78, 95% CI -1.23 to -0.33; p < 0.001). There was greater 4-year decline among diabetics (age and treatment-adjusted composite z score: NG -0.05, 95% CI -0.16 to 0.05; IFG 0.11, 95% CI -0.53 to 0.75; diabetics -1.00, 95% CI -1.50 to -0.50; p = 0.001). Further adjustment for education, race, and depression led to similar results. Risk of developing cognitive impairment among women with IFG or diabetes was increased by almost twofold (age and treatment-adjusted OR = 1.64; 95% CI 1.03 to 2.61 for IFG; OR = 1.79; 95% CI 1.14 to 2.81 for diabetics).
Diabetic as well as pre-diabetic women have impaired cognitive performance and greater risk of developing cognitive impairment.
Summary
There is limited wrist fracture information on men. Our goal was to calculate frequency and identify risk factors for wrist fracture in the Osteoporotic Fractures in Men (MrOS) study. We ...confirmed that fracture history and certain medications are predictors, and identified novel predictors including markers of kidney function and physical performance.
Introduction
To calculate the incidence of wrist fractures and their risk factors in older community-dwelling men from the US Osteoporotic Fractures in Men (MrOS) study.
Methods
Using triannual postcards, we identified incident wrist fractures (centrally confirmed by radiology) in men aged ≥ 65. Potential risk factors included the following: demographics, lifestyle, bone mineral density (BMD), selected medications, biomarkers, and physical function and performance measures. Both baseline and time-varying models were adjusted for age, race/ethnicity, MrOS geographic location, and competing mortality risks.
Results
We observed 97 incident wrist fractures among 5875 men followed for an average of 10.8 years. The incidence of wrist fracture was 1.6 per 1000 person-years overall and ranged from 1.0 among men aged 65–69 to 2.4 among men age ≥ 80. Significant predictors included the following: fracture history after age 50 hazard ratio (95% CI): 2.48 (1.65, 3.73), high serum phosphate 1.25 (1.02, 1.53), use of selective serotonin receptor inhibitor (SSRI) 3.60 (1.96, 6.63), decreased right arm BMD 0.49 (0.37, 0.65) per SD increase, and inability to perform the grip strength test 3.38 (1.24, 9.25). We did not find associations with factors commonly associated with wrist and other osteoporosis fractures like falls, diabetes, calcium and vitamin D intake, and alcohol intake.
Conclusions
Among these older, community-dwelling men, we confirmed that fracture history is a strong predictor of wrist fractures in men. Medications such as SSRIs and corticosteroids also play a role in wrist fracture risk. We identified novel risk factors including kidney function and the inability to perform the grip strength test.
Summary
In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over ...4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss.
Introduction
Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men.
Methods
Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4.
Results
Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm
2
) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss.
Conclusion
Use of ACE inhibitors but not ARB may marginally increase bone loss in older men.
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