Subjects
This cross-sectional study was conducted as part of the China National Diabetes and Metabolic Disorders Study [9]. We used a multistage, stratified sampling method to select a representative sample of persons 18 years of age or older in the general population. The sampling process was stratified according to geographic region, degree of urbanization and economic development status. In the first stage of sampling, the whole Sichuan province was stratified into urban and rural areas. Two sample points from urban areas and three from rural areas were selected to be representative of the geographic and economic characteristics in their regions. In the second stage, 2 street districts or rural villages were randomly selected from each sample point, respectively. Primary sampling units were street districts in urban areas and hamlets in rural sample points. In the third stage, one participant was selected from a randomly selected household in the primary sampling units. Simple random sampling methods were used at each stage. A total of 3514 subjects, including 1400 men and 2114 women, aged 18–76 years, participated in this survey between June and September 2007. Of the 3514 participants, 2347 with NGT [fasting plasma glucose (FPG) < 109.8 mg/dl, and 2-h post oral glucose tolerance test plasma glucose < 140.4 mg/dl] [10], and complete data were included in this study. Subjects with diabetes or prediabetes [including isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or IFG plus IGT] were excluded. After enrollment, subjects were stratified by sex. There were 2347 subjects ( 893 males and 1454 females),out of which there were 349 postmenopausal women. At present 45 subjects were on diuretics, 78 were on calcium channel blocker (CCB) and 53 others were on Angiotensin-Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blocker (ARB) therapy.
The study was approved by the Drugs/Medical Apparatus & Instruments Ethics Committee at China Japan Friendship Hospital (07020470055), and all subjects gave their informed consent. This study was registered on the Chinese clinical trial registry (#TR-CCH-Chi CTR-CCH-00000361).
Study design
A standard questionnaire was administered by trained staff to participants to record demographic characteristics and lifestyle risk factors [11]. Blood pressure, body weight, height, waist and hip circumference, body mass index (BMI), and waist/hip ratio (WHR) were measured and calculated using standard methods, as previously described [9]. Participants were instructed to maintain their usual physical activity and diet for at least 3 days before undergoing an OGTT. After an overnight fast ≥ 10 h, a venous blood specimen was collected to measure FPG, fasting insulin and blood lipids (including TC, TG, LDL-C, and HDL-C). Blood samples were also drawn at 30 and 120 min after a 75 g glucose load to measure glucose and insulin concentrations. The blood samples were placed in an ice box and transported to the laboratory of endocrinology and metabolism at West China Hospital, Sichuan University, for analysis. Plasma glucose levels were measured using a hexokinase enzymatic method. Insulin was measured by a radioimmunoassay with human insulin as a standard (Linco, St Charles, MO). TG, TC, LDL-C, and HDL-C levels were determined enzymatically. β cell function was calculated from insulin and glucose levels determined at 0 and 30 min using the following equation: (ΔI30 / ΔG30) / HOMA-IR, where the incremental glucose (ΔG30) and insulin (ΔI30) responses were calculated as the difference in values between 30 and 0 min. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FPG and fasting insulin levels as described by Matthews et al. [12] using the equation: (FPG × fasting insulin) / 22.5.
Statistical analysis
All analyses were performed using SPSS software version 16.0 (SPSS Inc., Chicago, IL). Since the distributions of fasting insulin, 0.5-h insulin, 2-h insulin, and TG were skewed, these parameters were logarithmically transformed before statistical analysis. Clinical and biochemical characteristics were compared using Student’s t test or χ
2 tests. Sex-specific mean values of β cell function were calculated for 10 mg/dl cut-off levels of TC (< 120, 120–139.9, 140–159.9, 160–179.9, 180–199.9, 200–219.9, and >220 mg/dl; n = 47, 104, 173, 194, 158, 124, and 93, respectively, for men; n = 65, 147, 319, 328, 264, 172, and 159, respectively, for women), for 25 mg/dl cut-off levels of TG (< 74.9, 75–99.9, 100–124.9, 125–149.9, 150–174.9, 175–199.9, and > 200 mg/dl; n = 165, 193, 157, 103, 82, 68, and 125, respectively, for men; n = 364, 375, 260, 156, 106, 52, and 141, respectively, for women), for 10 mg/dl cut-off levels of HDL-C (< 29.9, 30–39.9, 40–49.9, 50–59.9, 60–69.9, and > 70 mg/dl; n = 29, 201, 335, 205, 88, and 35, respectively, for men; n = 30, 204, 405, 444, 247, and 124, respectively, for women), for 15 mg/dl cut-off levels for LDL-C (< 84.9, 85–99.9, 100–114.9, 115–129.9, 130–144.9, 145–159.9, and > 160 mg/dl; n = 192, 166, 150, 132, 95, 74, and 84, for men; n = 360, 315, 281, 220, 110, 94, and 74, respectively, for women), for 0.5 unit cut-off levels of TC/HDL ratio (< 2.49, 2.5–2.99, 3.0–3.49, 3.5–3.99, 4.0–4.49, 4.5–4.99, and >5.0; n = 59, 138, 191, 180, 125, 90, and 110, respectively, for men; n = 167, 316, 357, 241, 150, 111,and 112, respectively, for women), for 1 unit cut-off levels of TG/HDL ratio (< 1.49, 1.5–2.49, 2.5–3.49, 3.5–4.49, 4.5–5.49, and > 5.5; n = 197, 262, 172, 102, 49, and 111, respectively, for men; n = 482, 489, 196, 136, 65, and 86, respectively, for women), and for 10-year age groups (< 30, 30–39, 40–49, 50–59, 60–69, and >70 years; n = 193, 229, 145, 151, 145, and 30, respectively, for men; n = 292, 355, 303, 265, 191, and 48, respectively, for women). Multiple linear regression analyses were used to examine the relationship between β cell function as the dependent variable and blood lipid levels as independent variables. Standardized coefficients (β) were determined after adjusting for age, family history of diabetes, level of activity, BMI, smoking, and systolic blood pressure (SBP). Multiple linear regression was also used to examine the relationship between β cell function and age, adjusting for family history of diabetes, level of activity, BMI, smoking, and SBP. T tests were used to compare sex-specific β cell function among subjects in different age groups.