Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes
Hyperinsulinaemia-induced whole-body glucose uptake during a euglycaemic–hyperinsulinaemic clamp is partly mediated by increased capillary density. We hypothesised that physiological insulinaemia in response to a mixed meal may also enhance microvascular function, and that this may be impaired in insulin-resistant individuals and patients with type 2 diabetes.
Twelve men with uncomplicated type 2 diabetes, 13 with metabolic syndrome and 12 age-matched healthy normoglycaemic controls, mean age 57 ± 6 years, underwent skin capillary video microscopy before and 60 and 120 min following a standardised mixed meal to measure baseline capillary density (BCD) and capillary density during post-occlusive peak reactive hyperaemia (PRH), also termed capillary recruitment. Oral glucose insulin sensitivity (Matsuda index) and postprandial hyperglycaemia (2 h AUCglucose) were calculated.
Fasting BCD was similar among groups, but fasting PRH was lowest in diabetes (p < 0.05). Postprandially, both BCD and PRH increased in all groups (p < 0.001); however, the meal-related increase in BCD was significantly lower in diabetes and metabolic syndrome vs controls (both p < 0.05). At all time points, postprandial PRH was lower in both diabetes and metabolic syndrome vs controls (both p < 0.05). In pooled analysis, postprandial mean PRH correlated with Matsuda index (r = 0.386, p = 0.018) and inversely with 2 h AUCglucose (r = −0.336, p = 0.042).
Gradual deterioration in meal-related capillary recruitment was paralleled by decreasing insulin sensitivity and postprandial hyperglycaemia, as assessed in healthy normoglycaemic men, men with the metabolic syndrome and those with type 2 diabetes. These findings suggest that in both impaired glucose tolerance and in overt diabetes microvascular dysfunction might contribute to postprandial dysglycaemia.
- Baron, AD (1994) Hemodynamic actions of insulin. Am J Physiol 267: pp. E187-E202
- Barrett, EJ, Wang, H, Upchurch, CT, Liu, Z (2011) Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab 301: pp. E252-E263 CrossRef
- Serne, EH, Stehouwer, CD, Maaten, JC (1999) Microvascular function relates to insulin sensitivity and blood pressure in normal subjects. Circulation 99: pp. 896-902 CrossRef
- Serne, EH, Ijzerman, RG, Gans, RO (2002) Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia. Diabetes 51: pp. 1515-1522 CrossRef
- Jongh, RT, Serne, EH, Ijzerman, RG, Vries, G, Stehouwer, CD (2004) Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation 109: pp. 2529-2535 CrossRef
- Meijer RI, de Boer MP, Groen MR et al (2012) Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole body glucose uptake. Microcirculation 19:494–500
- Vincent, MA, Clerk, LH, Lindner, JR (2006) Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab 290: pp. E1191-E1197 CrossRef
- Keske, MA, Clerk, LH, Price, WJ, Jahn, LA, Barrett, EJ (2009) Obesity blunts microvascular recruitment in human forearm muscle after a mixed meal. Diabetes Care 32: pp. 1672-1677 CrossRef
- Serne, EH, Jongh, RT, Eringa, EC, Ijzerman, RG, Stehouwer, CD (2007) Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension 50: pp. 204-211 CrossRef
- Liu, Z, Liu, J, Jahn, LA, Fowler, DE, Barrett, EJ (2009) Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature. J Clin Endocrinol Metab 94: pp. 3543-3549 CrossRef
- Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes
Volume 56, Issue 3 , pp 583-587
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Capillary video microscopy
- Glucose tolerance
- Insulin resistance
- Metabolic syndrome
- Microvascular function
- Mixed-meal test
- Postprandial hyperglycaemia
- Type 2 diabetes mellitus
- Industry Sectors
- Author Affiliations
- 1. Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
- 2. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands