Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 ...diabetes.
Patients with type 1 diabetes (
= 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths.
Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m
from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI <25 kg/m
, while BMI >25 kg/m
was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk.
Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.
Background Body mass index (BMI) may be a stronger risk factor for heart failure than for coronary heart disease in type 2 diabetes mellitus, but prior studies have not been powered to investigate ...the relative and absolute risks for acute myocardial infarction and heart failure in type 2 diabetes mellitus by BMI and glycemic level combined as compared with age- and sex-matched general population comparators. Methods and Results We identified 181 045 patients from The Swedish National Diabetes Registry, registered during 1998 to 2012 and 1538 434 general population comparators without diabetes mellitus, matched for age, sex, and county, all without prior major cardiovascular disease. Cases and comparators were followed with respect to the outcomes through linkage to the Swedish Inpatient Registry. Over a median follow-up time of 5.7 years, there were 28 855 acute myocardial infarction and 33 060 heart failure cases among patients and comparators. Excess risk (above that of comparators in whom no data on hemoglobin A1c and BMI was available), incidence rates and hazard ratios for heart failure were substantially higher among the obese patients compared with those with low BMI, where very obese patients (BMI ≥40 kg/m
) who also had poor glycemic control, suffered a 7-fold risk of heart failure versus comparators (reference level). By contrast, for acute myocardial infarction, the highest absolute and relative risks were found among patients with poor glycemic control, with no additional risk conferred by increasing BMI. Conclusions BMI is a strong independent risk factor for heart failure but not for acute myocardial infarction among patients with type 2 diabetes mellitus.
Type 2 diabetes is strongly associated with obesity, but the mortality risk related to elevated body weight in people with type 2 diabetes compared with people without diabetes has not been ...established.
We prospectively assessed short- and long-term mortality in people with type 2 diabetes with a recorded diabetes duration ≤5 years identified from the Swedish National Diabetes Registry between 1998 and 2012 and five age- and sex-matched control subjects per study participant from the general population.
Over a median follow-up of 5.5 years, there were 17,546 deaths among 149,345 patients with type 2 diabetes (mean age 59.6 years 40% women) and 68,429 deaths among 743,907 matched control subjects. Short-term all-cause mortality risk (≤5 years) displayed a U-shaped relationship with BMI, with hazard ratios (HRs) ranging from 0.81 (95% CI 0.75-0.88) among patients with diabetes and BMI 30 to <35 kg/m
to 1.37 (95% CI 1.11-1.71) with BMI ≥40 kg/m
compared with control subjects after multiple adjustments. Long-term, all weight categories showed increased mortality, with a nadir at BMI 25 to <30 kg/m
and a stepwise increase up to HR 2.00 (95% CI 1.58-2.54) among patients with BMI ≥40 kg/m
, that was more pronounced in patients <65 years old.
Our findings suggest that the apparent paradoxical findings in other studies in this area may have been affected by reverse causality. Long-term, overweight (BMI 25 to <30 kg/m
) patients with type 2 diabetes had low excess mortality risk compared with control subjects, whereas risk in those with BMI ≥40 kg/m
was substantially increased.
Delayed Transcapillary Delivery of Insulin to Muscle Interstitial Fluid After Oral Glucose Load in Obese Subjects
Mikaela Sjöstrand ,
Soffia Gudbjörnsdottir ,
Lena Strindberg and
Peter Lönnroth
From ...the Lundberg Laboratory for Diabetes Research, University Hospital, Göteborg, Sweden
Address correspondence and reprint requests to Mikaela Sjöstrand, MD, Lundberg Laboratory for Diabetes Research, Sahlgrenska
University Hospital, S-413 45 Göteborg, Sweden. E-mail: mikaela.sjostrand{at}medic.gu.se
Abstract
Obese subjects exhibit a delay in insulin action and delivery of insulin to muscle interstitial fluid during glucose/insulin
infusion. The aim of the present study was to follow the distribution of insulin to skeletal muscle after an oral glucose
load in obese subjects. We conducted an oral glucose tolerance test (OGTT) in 10 lean and 10 obese subjects (BMI 23 ± 0.6
vs. 33 ± 1.2 kg/m 2 ; P < 0.001). Insulin measurements in muscle interstitial fluid were combined with forearm arteriovenous catheterization and
blood flow measurements. In the obese group, interstitial insulin was significantly (35–55%) lower than plasma insulin ( P < 0.05) during the 1st h after the OGTT, whereas in lean subjects, no significant difference was found between interstitial
and plasma insulin levels during the same time period. The permeability surface area product for glucose, representing capillary
recruitment, increased in the lean group ( P < 0.05) but not in the obese group (NS). Obese subjects had a significantly higher plasma insulin level at 90–120 min after
oral glucose (398 ± 57 vs. 224 ± 37 pmol/l in control subjects; P < 0.05). The significant gradient between plasma insulin and muscle interstitial insulin during the first hour after OGTT
suggests a slow delivery of insulin in obese subjects. The hindered transcapillary transport of insulin may be attributable
to a defect in insulin-mediated capillary recruitment.
OGTT, oral glucose tolerance test
PS, permeability surface area product
Footnotes
Accepted September 13, 2004.
Received February 25, 2004.
DIABETES
This Swedish National Diabetes Register study showed that mortality varies greatly among patients with type 2 diabetes, as compared with the general population. There is excess risk in large patient ...groups, yet lower risks of death depending on age, glycemic control, and renal complications.
The global burden of diabetes has risen dramatically over the past two decades and is expected to affect more than 500 million adults by 2030, with most having type 2 diabetes.
1
Myocardial infarction is the most common cause of death in these patients.
2
,
3
Although factors that are known to reduce the risk of myocardial infarction,
2
,
4
,
5
including the use of lipid-lowering and antihypertensive medications and better glycemic control over time,
6
–
8
have been noted in persons with type 2 diabetes, an excess risk of death still exists.
9
Population-based studies have generally not evaluated the excess risks of death . . .
In this study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole) were found to have a risk of death from any cause or from cardiovascular causes that ...was twice as high as that for matched controls.
Type 1 diabetes is associated with a substantially increased risk of premature death as compared with that in the general population.
1
–
8
Among persons with diabetes who are younger than 30 years of age, excess mortality is largely explained by acute complications of diabetes, including diabetic ketoacidosis and hypoglycemia
7
–
9
; cardiovascular disease is the main cause of death later in life.
7
–
9
Improving glycemic control in patients with type 1 diabetes substantially reduces their risk of microvascular complications and cardiovascular disease.
10
,
11
Accordingly, diabetes treatment guidelines emphasize good glycemic control,
12
–
15
which is indicated by the glycated hemoglobin level, . . .
Aims
To describe trajectories for metabolic risk factors for type 2 diabetes (T2D) up to 25 years prior to diagnosis and to estimate the absolute 20‐year risk for T2D based on a simple set of ...commonly measured key risk factors.
Methods
From the Swedish AMORIS cohort we included 296 428 individuals with data on fasting glucose obtained in health examinations during 1985–1996 (baseline period). All participants were followed until 2012 for development of incident T2D. The 20‐year T2D risk based on age, sex, body mass index (BMI), fasting glucose and triglycerides was estimated. Trajectories for biomedical risk factors of T2D starting from >20 years before diagnosis and including fasting glucose, triglycerides and BMI were evaluated according to yearly means for cases and controls.
Results
We identified 28 244 new T2D cases during the study period, with an average 20‐year risk of 8.1%. This risk was substantially increased in overweight and obese participants and those with elevated fasting glucose and triglyceride levels, in both men and women. T2D cases had higher mean BMI and fasting glucose and triglyceride levels compared with controls >20 years before diagnosis and the difference in fasting glucose levels increased over time.
Conclusions
Development of T2D is associated with subtle elevations in glucose and lipid levels >20 years before diagnosis. This suggests that diabetogenic processes tied to chronic insulin resistance operate for decades prior to the development of T2D. A simple risk classification can help in early identification of individuals who are at increased risk.
Introduction
Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the ...adherence to and non-persistence with LLT.
Methods
This was a nationwide register-based cohort study that included 6192 individuals with T1D aged ≥ 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into ≤ 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months.
Results
Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio (OR 1.30,
p
< 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05,
p
= 0.0005 and OR 0.95,
p
= 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93,
p
= 0.0005) and discontinued LLT more often than the latter (OR 1.06,
p
= 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often.
Conclusion
Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment.
ObjectivesTo analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes ...mellitus.DesignCohort study.SettingNational population-based cohort of Swedish patients with type 2 diabetes mellitus.Participants86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007–2010, 87% for primary prevention.Exposure and outcome measuresRefill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%–40%, 41%–60%, 61%–80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics.ResultsThe hazard ratios for CVD ranged 1.33–2.36 in primary prevention patients and 1.19–1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001).ConclusionsHigher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.
Purpose
This study aimed to describe and compare refill adherence and persistence to lipid‐lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD).
Methods
We ...followed 97 595 patients (58% men; 23% with previous CVD) who were 18 years of age or older when initiating lipid‐lowering medicines in 2007–2010 until first fill of multi‐dose dispensed medicines, death, or 3 years. Using personal identity numbers, we linked individuals' data from the Swedish Prescribed Drug Register, the Swedish National Diabetes Register, the National Patient Register, the Cause of Death Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. We assessed refill adherence using the medication possession ratio (MPR) and the maximum gap method, and measured persistence from initiation to discontinuation of treatment or until 3 years after initiation. We analyzed differences in refill adherence and persistence by previous CVD in multiple regression models, adjusted for socioeconomic status, concurrent medicines, and clinical characteristics.
Results
The mean age of the study population was 64 years, 80% were born in Sweden, and 56% filled prescriptions for diabetes medicines. Mean MPR was 71%, 39% were adherent according to the maximum gap method, and mean persistence was 758 days. Patients with previous CVD showed higher MPR (3%) and lower risk for discontinuing treatment (12%) compared with patients without previous CVD (P < 0.0001).
Conclusions
Patients with previous CVD were more likely to be adherent to treatment and had lower risk for discontinuation compared with patients without previous CVD.
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