Background: The metabolic syndrome is an importantclusterofcoronaryheartdiseaseriskfactorswithcommon insulin resistance. The extent to which the metabolic syndrome is associated with demographic and potentially modifiable lifestyle factors in the US population is unknown. Methods: Metabolic syndrome–associated factors and prevalence, as defined by Adult Treatment Panel III criteria,wereevaluatedinarepresentativeUSsampleof3305 black,3477MexicanAmerican,and5581whitemenand nonpregnantorlactatingwomenaged20yearsandolder who participated in the cross-sectional Third National Health and Nutrition Examination Survey. Results: The metabolic syndrome was present in 22.8% and 22.6% of US men and women, respectively (P=.86). The age-specific prevalence was highest in Mexican Americans and lowest in blacks of both sexes. Ethnic differences persisted even after adjusting for age, body mass index, and socioeconomic status. The metabolic syndrome was present in 4.6%, 22.4%, and 59.6% of normal-weight, overweight, and obese men, respectively, and a similar distribution was observed in women. Older age, postmenopausal status, Mexican American ethnicity, higher body mass index, current smoking, low household income, high carbohydrate intake, no alcohol consumption, and physical inactivity were associated with increased odds of the metabolic syndrome.

Prevalence and Associated Risk Factor Findings in the US Population From the Third National Health and Nutrition Examination Survey, 1988-1994

Coronary heart disease (CHD) is the leading cause of death in the United States.1 Factors associated with an increased risk of developing CHD that tend to cluster in individuals include older age, high blood pressure, a low level of high-density lipoprotein (HDL) cholesterol, a high triglyceride level, a high plasma glucose concentration, and obesity.2 These associated risk factors have been called syndrome X,3 the insulin resistance syndrome,4 or the metabolic syndrome.5

The mechanisms underlying the metabolic syndrome are not fully known; however, resistance to insulin-stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors.3,6,7 Insulin resistance is thought to be primarily due to obesity or an inherited genetic defect.8 As the prevalence of obesity increases in the United States, the prevalence of the metabolic syndrome may be expected to increase markedly. Estimates of the prevalence of the metabolic syndrome have varied substantially in part because of the variability of evaluated populations and of diagnostic criteria.9

The recent Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATP III) included clinical diagnosis guidelines for the metabolic syndrome.10 Compared with findings from earlier studies3-5 and World Health Organization guidelines, the new ATP III defines criteria readily measured in clinical practice. These consensus-generated guidelines provide the opportunity to assess the overall prevalence of the metabolic syndrome in the US population according to an accepted standard definition. In an initial study, Ford et al11 reported un-adjusted and age-adjusted metabolic syndrome prevalences of 21.8% and 23.7%, respectively, for the US population. The objectives of this study are to examine the prevalence of the metabolic syndrome by ethnicity, age, body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters), socioeconomic status, and lifestyle factors.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/215123/ioi20116_427_436.pdf

The Metabolic Syndrome: Prevalence and Associated Risk Factor Findings in the US Population From the Third National Health and Nutrition Examination Survey, 1988-1994

Antidiabetic plants and their active constituents.

CONTEXT
Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes.


OBJECTIVE
To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes.


DATA SOURCES
A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts.


STUDY SELECTION
Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline.


DATA EXTRACTION AND DATA SYNTHESIS
Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria.


RESULTS
The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon.


CONCLUSION
Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

Active Smoking and the Risk of Type 2 Diabetes

ContextObservational studies have suggested an association between active smoking and the incidence of type 2 diabetes.ObjectiveTo conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes.Data SourcesA search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts.Study SelectionStudies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline.Data Extraction and Data SynthesisTwo authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria.ResultsThe search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (≥20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon.ConclusionActive smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

Active Smoking and the Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis

. Objectives. The acute effect of smoking and snuffing on insulin sensitivity was studied in a group of healthy habitual smokers.

Design The euglycaemic clamp technique was combined with the subcutaneous injection of a bolus (0.1 U kg−1) of fast-acting insulin (Actrapid®). Randomized subjects smoked either one cigarette per hour for 6 h, took one bag-packed snuff per hour for 6 h or refrained from nicotine for 48 h before as well as during the clamp.

Subjects. Seven healthy smokers, four females and three males, of normal weight (BMI, mean ± SKM. 21 ± 0.7 kg m−2 with a range of 18.6–23.9), aged 31 ± 2 years (range 24–35 years), who had consumed at least 20 cigarettes per day for at least 5 years were studied. They were recruited through an advertisement in a newspaper. Results. The steady-state plasma nicotine levels were similar during smoking and snuffing. The insulin and glucose levels were also similar during all three clamps. Smoking, but not snuffing, impaired insulin action (P < 0.05) mainly due to a lower peripheral glucose uptake. The mean growth hormone levels during the 6-h study were more than doubled during smoking (P < 0.01) while no significant differences were seen in the other counter-regulatory hormones.

Conclusion. Smoking (also in habitual smokers) acutely impairs insulin action and leads to insulin resistance. Thus, smoking can be of importance for the development of the insulin resistance syndrome associated with risk for cardiovascular disease.

Smoking induces insulin resistance--a potential link with the insulin resistance syndrome.

In a double-blind, cross-over, placebo-controlled trial, the effect of 26 weeks of replacement therapy with recombinant human growth hormone (rhGH) on insulin sensitivity and glucose metabolism in nine patients with adult-onset growth hormone deficiency was studied with a euglycemic clamp. Glucose production and utilization were studied with d-(3-3H)-glucose infusions. Comparisons were made with placebo treatment for 6 and 26 weeks, respectively. GH therapy for 6 weeks increased fasting plasma concentrations of glucose and insulin. However, after 26 weeks of GH treatment, no significant changes in glucose or insulin concentrations were recorded. GH treatment induced a marked change in insulin action evident after 6 weeks of therapy as shown by lower glucose infusion rates (GIRs) during the clamp compared with placebo treatment (2.6 ± 0.4 v 4.1 ± 0.7 mg · kg−1 · min−1). This change in insulin action was due to a decreased insulin effect on glucose utilization. After 26 weeks of GH therapy, there was no significant difference in GIRs. During placebo treatment, insulin sensitivity and insulin, glucose, and nonesterified fatty acid (NEFA) concentrations were unchanged compared with concentrations measured before the study. Thus GH replacement therapy induces a change in insulin action in GH-deficient individuals. Whether this change represents a decrease in insulin action (ie, insulin resistance) or a restoration of action to normal is presently unclear, since a healthy control group was not included in the study. During long-term treatment, the present study suggests that the change in insulin action can be reversed, probably secondarily to changes in body composition.

Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency

To evaluate the interstitial insulin and inulin concentrations, 20-min microdialysis samples from the abdominal subcutaneous tissue were obtained by using two 45-mm polypropylene dialyzing tubes (o.d. approximately 0.5 mm, pore size 0.2 micron) during a euglycemic hyperinsulinemic (120 mU.m-2 x min-1) clamp (n = 9) or during a constant inulin infusion (n = 5). After in situ calibration of the microdialysis catheters during steady-state conditions, interstitial and plasma insulin concentrations were estimated to 654 +/- 102 and 1176 +/- 66 pM, respectively, i.e., a 44% difference (P < 0.001). A doubling of the insulin infusion rate (240 mU.m-2 x m-1), leading to supraphysiological plasma insulin levels, raised the interstitial insulin concentrations markedly slower (approximately 20 min) than in plasma. Moreover, at steady state the concentration difference in the two compartments prevailed even during the high insulin infusion rate (55% difference, P < 0.01). In contrast, the interstitial inulin levels were similar to the plasma concentrations in subjects given a constant inulin infusion. Thus, the data suggest the presence of an endothelial barrier for insulin in the subcutaneous tissue. This barrier, in combination with tissue clearance of insulin, leads to lower insulin levels and altered kinetics with a slower rise in the interstitial fluid compared with plasma.

Measurement by Microdialysis of the Insulin Concentration in Subcutaneous Interstitial Fluid: Importance of the Endothelial Barrier for Insulin

The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU·kg−1·min−1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol·l−1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36±0.2 mU·l−1). Peak growth hormone levels were reached at 60 min (growth hormone 6mU·kg−1·h−1: 31±5; growth hormone 12 mU·kg−1·h−1: 52±4 and growth hormone 24 mU·kg−1·h−1: 102±8mU·l−1). The insulin-antagonistic effect of growth hormone started after ∼2 h, was maximal after 4–5 h (∼39% inhibition of glucose infusion rate between control and growth hormone 24 mU·kg−1·h−1) and lasted for 6–7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU·kg−1·h−1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU·kg−1·h−1 induced a smaller response with a duration of 1 h between 3–4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects. The effects starts after about 2–3 h, is maximal after 4–5 h and lasts for about 6–7 h. Both duration and inhibitory effect of growth hormone are related to the plasma levels, where a maximal effect is seen at about 50 mU·l−1 or higher.

https://link.springer.com/content/pdf/10.1007/BF00403286.pdf

Characterization of the insulin-antagonistic effect of growth hormone in man.

The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin-antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation.

/pdf/early-posthypoglycemic-insulin-resistance-in-man-is-mainly-kde8oa0ojq.pdf

J. Fowelin

Papers

Smoking induces insulin resistance--a potential link with the insulin resistance syndrome.

Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency

Measurement by Microdialysis of the Insulin Concentration in Subcutaneous Interstitial Fluid: Importance of the Endothelial Barrier for Insulin

Characterization of the insulin-antagonistic effect of growth hormone in man.

Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.