Insulin Resistance and the Risk of Stroke and Stroke Subtypes in the Nondiabetic Elderly

Q: What are the key findings of this study?

Fasting insulin levels and HOMA-IR were not associated with increased risk of any stroke or stroke subtypes in nondiabetic elderly.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Nondiabetic elderly free of prior stroke (n=5234). Intervention: Markers of insulin resistance (fasting insulin levels and HOMA-IR index) vs. Lower quartiles of fasting insulin or HOMA-IR / per SD increase. Primary outcome: First-ever stroke (any stroke, adjusted for age and sex per SD of log-transformed fasting insulin) (HR 0.94, 95% CI 0.85, 1.05).

Q: What does this research mean for the field?

Fasting insulin levels and HOMA-IR are not associated with risk of stroke or stroke subtypes in nondiabetic elderly individuals. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Renske G. Wieberdink; Peter J. Koudstaal; A. Hofman; Jacqueline C.M. Witteman; Monique M.B. Breteler; M. Arfan Ikram

doi:10.1093/aje/kws149

October 3, 2012American Journal of EpidemiologyOpen Access

Insulin Resistance and the Risk of Stroke and Stroke Subtypes in the Nondiabetic Elderly

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Key result

Fasting insulin and HOMA-IR show no association with incident stroke risk in nondiabetic elderly.

HR 0.94
95% CI 0.85, 1.05
n=5,234

Why the study?

Are markers of insulin resistance (fasting insulin levels and HOMA-IR) associated with the risk of incident stroke and stroke subtypes (cerebral infarction and intracerebral hemorrhage) in nondiabetic elderly individuals?

Study Design

Type

Cohort (n=5,234)

Multicenter

No

Structured PICO

Are markers of insulin resistance (fasting insulin levels and HOMA-IR) associated with the risk of incident stroke and stroke subtypes (cerebral infarction and intracerebral hemorrhage) in nondiabetic elderly individuals?

P

Population

5,234 nondiabetic adults aged 55 years or older (median age 67.9 years, 57.6% female) free of prior stroke from the population-based Rotterdam Study, followed for a median of 8.6 years.

E

Exposure

Elevated markers of insulin resistance measured from overnight fasting venous blood samples at baseline: natural log-transformed fasting serum insulin levels (pmol/L, per SD increase and across quartiles) and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR, calculated as [fasting insulin (mU/L) × fasting glucose (mmol/L)] / 22.5, per SD increase and across quartiles), as well as fasting serum glucose levels.

C

Comparator

Lowest quartile (Quartile 1) of fasting insulin (10-46 pmol/L), HOMA-IR (0.3-<1.6), or fasting glucose (3.7-<5.2 mmol/L), or continuous evaluation per standard deviation increase.

O

Outcome

Incident first-ever stroke (defined by WHO criteria as rapidly developing clinical signs of focal or global disturbance of cerebral function lasting ≥24 hours or leading to death with no apparent non-vascular cause) and stroke subtypes (cerebral infarction and intracerebral hemorrhage classified by neuroimaging) over a median follow-up of 8.6 years (42,806 person-years).hard clinical

Main Result

Hazard Ratio: 0.94 (95% CI 0.85–1.05)

In nondiabetic elderly individuals, fasting markers of insulin resistance (fasting insulin and HOMA-IR) and normoglycemic fasting glucose levels are not associated with an increased risk of stroke, cerebral infarction, or intracerebral hemorrhage, contrasting with the established stroke risk of overt diabetes mellitus.

Limitations

Excluded 2,477 participants due to incomplete data on fasting glucose or insulin levels, who were older and more often female, potentially introducing selection bias
Neuroimaging was not performed in all stroke cases, leaving 27% of strokes unclassified as either cerebral infarction or intracerebral hemorrhage
Fasting insulin levels were measured only once at baseline, precluding assessment of intraindividual fluctuations
Lack of postprandial insulin measurements to assess postprandial insulin resistance
Small number of intracerebral hemorrhage events (n = 42)
Exclusion of 2,477 participants due to incomplete data on fasting glucose or fasting insulin levels (who were older and more often female), potentially causing selection bias
Lack of neuroimaging in all stroke cases, resulting in 27% of strokes being classified as unspecified
Single baseline measurement of fasting insulin and glucose, preventing evaluation of intraindividual fluctuations over time
Absence of postprandial insulin measurements
Relatively small number of intracerebral hemorrhage events (n=42)

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Does not support insulin resistance markers for stroke risk assessment in nondiabetic elderly; leaves open their role beyond overt diabetes.

Abstract

Insulin resistance, which plays a key role in the development of diabetes mellitus, is a putative modifiable risk factor for stroke. The aim of this study was to investigate if markers of insulin resistance were associated with risk of stroke in the general elderly population. This study was part of the large population-based Rotterdam Study and included 5,234 participants who were aged 55 years or older and stroke free and diabetes free at baseline (1997-2001). Fasting insulin levels and homeostasis model assessment for insulin resistance were used as markers for insulin resistance. Cox regression was used to determine associations between insulin resistance markers and stroke risk, adjusted for age, sex, and potential confounders. During 42,806 person-years of follow-up (median: 8.6 years), 366 first-ever strokes occurred, of which 225 were cerebral infarctions, 42 were intracerebral hemorrhages, and 99 were unspecified strokes. Fasting insulin levels were not associated with risk of any stroke, cerebral infarction, or intracerebral hemorrhage. Homeostasis model assessment for insulin resistance, which almost perfectly correlated with fasting insulin levels, was also not associated with risk of stroke or stroke subtypes. In conclusion, in this population-based cohort study among nondiabetic elderly, insulin resistance markers were not associated with risk of stroke or any of its subtypes.

Discussion

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Cite This Study

Wieberdink et al. (2012) conducted a cohort in Nondiabetic elderly free of prior stroke (n=5,234). Markers of insulin resistance (fasting insulin levels and HOMA-IR index) vs. Lower quartiles of fasting insulin or HOMA-IR / per SD increase was evaluated on First-ever stroke (any stroke, adjusted for age and sex per SD of log-transformed fasting insulin) (HR 0.94, 95% CI 0.85, 1.05). Fasting insulin levels and HOMA-IR were not associated with increased risk of any stroke or stroke subtypes in nondiabetic elderly.

synapsesocial.com/papers/6a819441142aa74d5e58ba00 https://doi.org/10.1093/aje/kws149

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Insulin Resistance and the Risk of Stroke and Stroke Subtypes in the Nondiabetic Elderly

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Insulin Resistance and the Risk of Stroke and Stroke Subtypes in the Nondiabetic Elderly

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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