Evidence for a Circadian Rhythm of Insulin Sensitivity in Patients With NIDDM Caused by Cyclic Changes in Hepatic Glucose Production
Abstract
Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 ± 2.5) underwent hyperglycemic (11.1 mmol/l, ∼200 mg/dl) clamping for 72 h. Measured were serum insulin, free fatty acid (FFA), cortisol, and growth hormone concentrations and rates of insulin secretion, insulin clearance, and glucose infusion rate (GIR) needed to maintain hyperglycemia. In addition, five patients (three men and two women, BMI 32.6 ± 0.6) underwent hyperglycemic clamping for 24 h with hourly determinations of hepatic glucose production (HGP) and glucose disappearance rates (GRd). GIR, reflecting insulin sensitivity, changed rhythmically with a cycle duration of 22.9 ± 1.4 h and an amplitude of 47.8 ± 11.2%. GIR was lowest at 8:31 a.m. (±52 min) and highest at 7:04 p.m. (±58 min). Circadian changes in GIR were completely accounted for by changes in HGP, while GRd remained unchanged. Plasma levels of FFAs and cortisol also exhibited circadian fluctuations, and their blood levels correlated negatively with GIR (r = −0.72 and −0.64, respectively). We concluded that insulin sensitivity in patients with NIDDM changed with circadian (∼24 h) rhythmicity (decreasing during the night and increasing during the day). These changes were unrelated to blood levels of glucose and insulin, insulin clearance, exercise, food intake, and sleep. They were caused by circadian changes in HGP, which in turn were closely correlated with circadian changes in blood FFA and cortisol levels. We believe that recognition of these circadian changes has implications for the diagnosis and the treatment of patients with NIDDM.
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In people with type 2 diabetes, the degree of insulin resistance correlates with higher nocturnal NEFA levels.
“the degree of insulin resistance in patients with type 2 diabetes correlates with the elevation in nocturnal NEFA levels [30].”
From Sleep restriction increases free fatty acids in healthy men (2015) · cites this paper as [30]
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Should we listen to our clock to prevent type 2 diabetes mellitus?
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“Finally, it is important to note that circadian rhythms in insulin secretion are disrupted in states associated with metabolic disease such as obesity and T2DM [30,33], implying an intriguing possibility that loss of circadian rhythmicity in insulin secretion may serve as an early biomarker of β-cell dysfunction in T2…”
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BackgroundGlucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats
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Why Does Obesity Increase the Risk for Cardiovascular Disease?
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- Authors
- Boden, G., Chen, X., & Urbain, J. L.
- Affiliations
- Divisions of Endocrinology, Diabetes and Metabolism and Nuclear Medicine Philadelphia, Pennsylvania
- Temple University (US)
- Corresponding author
- Boden, Guenther
- ORCID
- Chen, Xinhua
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1996-08-01
- Volume
- 45
- Issue
- 8
- Pages
- 1044-1050
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2138487775
- Cited by
- 228
- References
- 0
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 15 · 2019: 4 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 15 · 2014: 18 · 2013: 10 · 2012: 7
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01ag007988-10, 5r01aa010221-03)
- National Institute on Alcohol Abuse and Alcoholism (R01-AA-10221)
- National Institute on Aging (R01-AG07988)
- National Center for Research Resources (RR-349)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin sensitivity, circadian rhythm, type 2 diabetes, hepatic glucose production, glucose infusion rate, glucose disappearance rate, free fatty acids, cortisol, insulin secretion, insulin clearance
- MeSH terms
- Alanine, Circadian Rhythm, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Glucagon, Glucose, Humans, Hydrocortisone, Insulin, Lactates, Liver, Male, Middle Aged, Sleep, Growth Hormone
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