Continuous Infusion Of Glucose With Model Assessment Research Articles

Association of Gestational Diabetes with Parental Diabetic Mellitus and Impaired Glucose Tolerance: A Cross-Sectional Study

Aim: To determine the association of gestational diabetes with parental diabetic mellitus and impaired glucose tolerance Study design: A cross-sectional study Place and Duration: This study was conducted at Jahra Hospital Kuwait from February 2021 to February 2022 Methodology: This study includes 100 women with gestational diabetes. They were aged 35 (±5) years. They were tested by fasting plasma glucose (fpg). There were 61 women who either had diabetes or fasting hyperglycemia (fpg = >5.4 millimole/l). A total of 35 women had their parents alive. Of these 35 women’s parents, 14 women’s parents agreed to test their metabolism. Their metabolism was tested by CIGMA (continuous infusion of glucose with model assessment). Results: Among those 14 families, 7 probands had diabetes and the other 7 had impaired glucose tolerance (IGT). The women were aged 36 (±4) years with a BMI of 27 (±5) kilograms/m2. The parents were aged 63 (±5) with a BMI of 30 (±5) kilograms/m2. The presence of glucose intolerance defined their affection status (an age and obese matched population with fpg or post-infusion attained plasma glucose levels greater than 3 standard deviation). Among those 14 families, 5 probands did not have any parent affected, which represents 35.7%, 3 probands had both parents affected, which represents 21.4%, and 6 probands had only 1 parent affect, which represents 42.9%. Only 3 of proband’s parents were affected by diabetes as explained by WHO criteria. Practical implication This paper outlines some of the growing evidence showing pregnant women with gestational diabetes mellitus are more likely to give birth to diabetic mothers. These preliminary findings' are provocative implications to encourage additional research. Conclusion: In conclusion, examining women with gestational diabetes, who have both parents available for this research, helps to find probands with IGT or diabetes. Those who had neither parents impacted with diabetes nor IGT were representing a significant portion which was much the same as elementary families of NIDDM. Keywords: diabetes mellitus, gestational diabetes, parents, impaired glucose tolerance

Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I

Blocking the renin-angiotensin system (RAS) may reduce the risk of developing type-2 diabetes, but data are inconclusive and the mechanisms involved are unclear. RAS and RAS inhibition also influence the IGF-I system, which is important in glucose homeostasis. We investigated the effects of the angiotensin-receptor antagonist, losartan, on insulin resistance and IGF-I levels In this hypothesis-generating study, five individuals with impaired fasting glucose received 100 mg losartan during 8 weeks. Before and after the treatment period, insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA), as well as the 2-h continuous infusion of glucose with model assessment (CIGMA). Furthermore, serum levels of free and total IGF-I, IGF-binding protein-3 (IGFBP-3), lipids and HbAlc were measured. After the treatment period, the HOMA score for insulin resistance had decreased from 5.3+/-1.1 to 3.7+/-0.9 (P=0.004) and the 2-h CIGMA score from 23.4+/-3.1 to 15.9+/-2.1 (P=0.07). The serum levels of free IGF-I had increased from 57+/-18.8 to 134+/-31.3 pmol/l (P=0.04). In terms of percentage, the decrease of HOMA correlated with the increase in free IGF-I levels (Pearson's correlation coefficient r=-0.8; P=0.07). A trend in the same direction was observed with 2-h CIGMA. No differences were observed in lipids, total IGF-I, IGFBP-3 or HbAlc. Losartan raised serum levels of free IGF-I, which might contribute to the improvement of insulin resistance associated with losartan treatment. These observations, if confirmed in broader studies, will help our understanding of the pathogenesis of type-2 diabetes mellitus, as well as the role of angiotensin-receptor antagonists in its prevention.

The impact of insulin resistance on the outcome of laparoscopic ovarian electrocautery in infertile women with the polycystic ovary syndrome

In this study we assessed how insulin resistance affects pregnancy rates in infertile women with the polycystic ovary syndrome (PCOS) treated with laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the study in a consecutive fashion. Following the CIGMA (continuous infusion of glucose with model assessment) test, 28 women were classified as insulin resistant and 36 women as non-insulin resistant. After the ovarian electrocautery patients were observed for 12-18 months. If pregnancy did not ensue, they were referred for one or more cycles of in vitro fertilization (IVF). Following ovarian electrocautery the non-insulin-resistant women more frequently achieved a regular menstrual cycle and ovulation than the insulin-resistant PCOS women. Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a pregnancy versus only five (18%) of women in the insulin-resistant PCOS group. Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non-insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance may be an important marker of a poor outcome of treatment in PCOS infertility. Further studies are needed to evaluate the possible effect of treatment alternatives to alleviate the unfavorable influences of insulin resistance and hyperinsulinemia on ovulation induction in PCOS women.

Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus

The purpose of this study was to evaluate insulin sensitivity ,β-cell function and islet-cell-directed autoimmunity in pregnant women with normal glucose tolerance and gestational diabetes mellitus(GDM). A total of 21 women with normal glucose tolerance and 21 women with GDM were evaluated at 24-36 weeks' gestation. Insulin resistance and β-cell function were evaluated using the continuous infusionof glucose with model assessment (CIGMA) method ,which aims to give a near-physiological stimulus and to evaluate the endogenous insulin and glucose response. Islet-cell autoantibody was positive in onewoman with GDM ,and glutamic acid decarboxylase autoantibodies were negative in both groups. The calculated CIGMA insulin resistance (CIGMA IR) was 2.04 ± 1.74 and 1.08 ± 1.22 in patientswith GDM and in control subjects ,respectively (p < 0.05). CIGMA percentage β-cell values were 64.04 ± 44.55% and 87.07 ± 52.77% in patients with GDM and control subjects ,respectively(p > 0.05). Decreased insulin sensitivity in late pregnancy was more evident in lean GDM subjects with mild hyperglycemia who did not require insulin therapy ,and β-cell function was partially preservedin this group of patients.

Impact of Insulin Resistance on Pregnancy Complications and Outcome in Women with Polycystic Ovary Syndrome

The aim of the study was to determine the risk of developing gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH)/pre-eclampsia in a cohort of pregnant women with the polycystic ovary syndrome (PCOS) and known insulin sensitivity status. Pregnancies and neonatal outcome were recorded in a prospective cohort study comprising 29 non-insulin-resistant PCOS women, 23 insulin-resistant PCOS women and a control group of 355 women who had conceived after assisted reproduction. Hypertension, pre-eclampsia and GDM were recorded as well as pregnancy duration, method of delivery and birth weight. The frequency of hypertension was significantly elevated in PCOS women (11.5%) compared to controls (0.3%), p < 0.01. However, the frequency of pre-eclampsia was significantly elevated only in the insulin resistant PCOS women (13.5%) compared to controls (7.0%), p < 0.02. GDM was significantly more frequent in PCOS women (7.7%) than controls (0.6%), p < 0.01. Insulin resistance prior to pregnancy, determined by continuous infusion of glucose with model assessment (CIGMA) test, did not further increase the frequency of GDM. Newborns from PCOS pregnancies were significantly more often delivered by Caesarean section than controls (40.3 vs. 27.3%, p < 0.05) and transferred to neonatal intensive care unit more often than controls (19.2 vs. 9.0%, p < 0.01). Thus we show that the frequencies of pre-eclampsia and GDM are increased in PCOS pregnancies.

Circulating ghrelin levels in patients with polycystic ovary syndrome.

The syndrome of polycystic ovaries (PCOS) is associated with adiposity and metabolic changes predisposing to insulin resistance and diabetes mellitus. Because the recently discovered GH secretagogue, ghrelin, is intimately involved in the control of appetite and weight regulation, we studied ghrelin levels in a group of 26 otherwise healthy women with PCOS. They were compared with 61 healthy female control subjects and 5 gastrectomized women. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and continuous infusion of glucose with model assessment (CIGMA) in all patients. In PCOS women, serum ghrelin levels were significantly lower than in healthy lean or obese controls (P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels were significantly lower and indistinguishable from the low levels found in the gastrectomized women. There was a close correlation of ghrelin to insulin sensitivity (HOMA, r(2) = 0.330, P < 0.002; CIGMA, r(2) = 0.568, P < 0.0001). Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH ratio, to body mass index, or to fasting insulin and glucose concentrations. In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This suggests that ghrelin could be linked to insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50 ,55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis ,and an insulin resistance index (IR1) was obtained. Using insulin and glucose values at 60 min only ,a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition ,fasting insulin ,fasting C-peptide, fasting glucose ,fasting insulin : glucose ratio and fasting C-peptide : glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2, fasting glucose ,fasting insulin ,fasting insulin : glucose ratio ,fasting C-peptide : glucose ratio. IR2 had the highest correlation with IR1 (r =0.97 ,p < 0.001) and provided the best combination of sensitivity (82.9%) ,specificity (93.9%) ,positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion ,the simplified CIGMA test ,using insulin and glucose concentration at 60 min of glucose infusion only ,is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome.

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The meanconcentrations of glucose and insulin at 50 ,55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis ,and an insulin resistance index (IR1)was obtained. Using insulin and glucose values at 60 min only ,a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition ,fasting insulin ,fasting C-peptide,fasting glucose ,fasting insulin : glucose ratio and fasting C-peptide : glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2,fasting glucose ,fasting insulin ,fasting insulin : glucose ratio ,fasting C-peptide : glucose ratio. IR2 had the highest correlation with IR1 (r =0.97 ,p < 0.001)and provided the best combination of sensitivity (82.9%) ,specificity (93.9%) ,positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion ,the simplified CIGMA test ,using insulinand glucose concentration at 60 min of glucose infusion only ,is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.

Insulin secretion and sensitivity after simultaneous pancreas-kidney transplantation estimated by continuous infusion of glucose with model assessment.

Monitoring of insulin secretion and sensitivity after pancreas transplantation remains a practical problem. We introduced the simple structural model, continuous infusion of glucose with model assessment (CIGMA), to obtain insulin secretion and insulin sensitivity estimations after 35 successful simultaneous pancreas-kidney transplantations. Eighteen non-diabetic kidney transplant recipients were used as control group. The baseline characteristics were equal between the two groups except for higher fasting insulin levels in the pancreas transplant group. After the 1-hr CIGMA glucose load, the pancreas transplant group reached a mean +/- SD blood glucose of 8.2+/-1.7 mmol/L compared with 7.3+/-1.0 mmol/L in the control group (P = 0.05). Concurrent stimulated insulin and C-peptide levels were 48+/-28 mU/L and 2.3+/-0.9 nmol/L in the pancreas transplant group compared with 36+/-21 mU/L and 2.9+/-1.1 nmol/L in the control group (P = 0.1 and P = 0.03, respectively). Both the CIGMA estimation for secretion as well as the CIGMA estimation for sensitivity were lower in pancreas transplant group (P = 0.003 and P = 0.01, respectively). Mean +/- SE coefficients of variation for the model estimations were 15+/-4% for secretion and 17+/-6% for sensitivity. We conclude that CIGMA can be used clinically to evaluate carbohydrate metabolism in pancreas-kidney transplant recipients. These patients have a reduction in insulin secretory capacity and evidence of more insulin resistance than non-diabetic kidney transplant recipients.

The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome.

In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.

β-Cell function and insulin sensitivity in tropical calcific pancreatitis from North India

Tropical calcific pancreatitis (TCP) is a variant of chronic pancreatitis, occurring only in developing countries. It frequently leads to diabetes at a young age. To determine the pathogenesis of glucose intolerance, β-cell function and insulin sensitivity were measured in 11 TCP patients with normal glucose tolerance (TCP-NGT), six TCP patients with mild hyperglycemia [TCP-DM] median fasting plasma glucose, 6.1 mmol/L), and 16 healthy control subjects. The technique of continuous infusion of glucose with model assessment (CIGMA) was used to calculate β-cell function (%B) and insulin sensitivity (%S), based on plasma glucose and insulin levels achieved after an intravenous infusion of glucose. %S was similar in both groups of TCP patients and controls. In contrast, %B was significantly lower in TCP-DM patients (median, 53; interquartile range, 41 to 62) compared with controls (90; 65 to 143; P < .01) and with TCP-NGT patients (119; 91 to 159; P < .01). TCP-NGT and control subjects had similar β-cell function. Among patients with TCP, %B negatively correlated with the duration of pancreatitis ( r = −.63, P < .05). Our results suggest that patients with TCP develop diabetes due to a diminution in beta-cell function, and that insulin resistance does not play a significant role in its pathogenesis.

Relationship of insulin resistance to microvascular dysfunction in subjects with fasting hyperglycaemia.

Microvascular hyperaemia is decreased in subjects at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) who have fasting hyperglycaemia. Such microvascular abnormalities may be involved in the pathogenesis of diabetic microangiopathy. To investigate the relationship of reduced microvascular hyperaemia to metabolic and blood pressure abnormalities associated with the prediabetic state, we studied 24 subjects with fasting hyperglycaemia and 24 age- and sex-matched control subjects. The microvascular hyperaemic response to local heating of the skin on the dorsum of the foot measured by laser Doppler fluximetry was reduced in the subjects with fasting hyperglycaemia (1.18 [0.87-1.83] volts vs 1.51 [1.30-2.14] volts normal subjects; p = 0.0002) and was negatively correlated with fasting plasma insulin concentration (Rs = 0.70; p = 0.001) and positively related to insulin sensitivity determined by continuous infusion of glucose with model assessment (CIGMA) (Rs = 0.52; p = 0.01), but showed no association with fasting plasma glucose, beta-cell function 24 h ambulatory blood pressure profiles or serum lipid concentrations. These results suggests that hyperinsulinaemia, as a result of insulin resistance, may have a detrimental effect on microvascular function in the prediabetic state.

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes.

Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (+/- SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5 < or = fpg < 7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m2. The parents were aged 62 (6) years and had BMI 29 (6) kg/m2 and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level > 2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We conclude that the study of women who have had gestational diabetes allows detection of probands with diabetes or impared glucose tolerance, who have both parents available for study.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of three methods for the quantification of β-cell function and insulin sensitivity

The purpose of this study was to compare two techniques for the quantification of β-cell function and insulin sensitivity. Sixteen subjects (2 with newly diagnosed non-insulin-dependent diabetes mellitus, 8 with impaired glucose tolerance (IGT) and 6 with normal glucose tolerance (NGT)), aged 40–65 years underwent an oral glucose tolerance test (OGTT), a continuous infusion of glucose with model assessment (CIGMA) and a hyperglycaemic clamp (10 mmol/l) in random order. As measures of β-cell function we used the clamp derived area under the curve from 0–10 min (first phase insulin response) and the mean insulin level during the last 20 min of the clamp (second phase insulin response). Insulin sensitivity was reflected by the ratio of the glucose infusion rate and the mean insulin level during the last 20 min of the clamp ( M I ratio). Measures for β-cell function and insulin sensitivity derived from OGTT and CIGMA appeared to correlate only moderately (0.5–0.7) with the corresponding clamp measures. It is concluded that OGTT and CIGMA derived measures of β-cell function and insulin sensitivity should be interpreted with caution.

Prednisolone enhances β-cell function independently of ambient glycemic levels in type II diabetes

This study examined the changes in β-cell response and insulin sensitivity induced by a single overnight dose of 15 mg prednisolone in eight type II diabetic subjects, seven nondiabetic normal controls, and eight subjects with a first-degree type II diabetic relative who were therefore at risk of developing diabetes. β-Cell secretion was assessed by use of the hyperglycemic clamp technique, and insulin sensitivity was assessed with the clamp and the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique. Subjects were studied in random order on two occasions, after placebo and after prednisolone administration. Normal subjects showed an increase of median fasting glucose level from 4.7 to 5.2 mmol · L −1 after prednisolone ( P < .02) and at-risk subjects showed an increase from 4.8 to 5.5 mmol · L −1 ( P < .005), whereas diabetic subjects showed no significant increase in median fasting plasma glucose level (7.0 mmol · L −1 after placebo and 6.3 mmol · L −1 after prednisolone). Six of these eight diabetic subjects showed a paradoxical decrease of fasting plasma glucose level after prednisolone therapy. All three groups showed a significant elevation of clamp steady-state plasma insulin levels following prednisolone, with a median percentage elevation of 46%, 66%, and 31% for normal, at-risk, and diabetic subjects, respectively. All three groups showed significant reduction in insulin sensitivity measured by CIGMA following prednisolone of 51%, 41%, and 25% of pre-prednisolone levels in normal, at-risk, and diabetic subjects, respectively, with a significantly greater reduction in normal subjects than in diabetics ( P < .02). Stimulation of insulin levels in the diabetic group, in the absence of an elevation of plasma glucose level and a minimal decrease in insulin sensitivity, suggests that prednisolone has an in vivo stimulatory effect on the β cell independent of changes in ambient glycemia and insulin sensitivity. The interaction between the different effects of prednisolone in nondiabetic groups was more complex, as fasting glucose levels were altered by prednisolone. The prednisolone-CIGMA test improved the distinction between normal and at-risk subjects, but the magnitude was not sufficient to be clinically useful.

Diet treatment of newly presenting type 2 diabetes improves insulin secretory capacity, but has no effect on insulin sensitivity.

Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l-1 at diagnosis and 8.5 mmol l-1 at 3 months (NS). Median fasting insulin was 9.3 mU l-1 at diagnosis and 11.7 mU l-1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l-1 at diagnosis and 0.64 nmol l-1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l-1 at diagnosis to 17 mU l-1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l-1 at diagnosis to 0.81 nmol l-1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26% at diagnosis to 37% at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (Rs = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity.

Hyperglycaemic progression in subjects with impaired glucose tolerance: association with decline in beta cell function.

Impaired glucose tolerance is associated with an increased risk of Type 2 diabetes. This prospective cohort study has examined the variables associated with hyperglycaemic progression in order to elucidate the aetiology of this deterioration. The 5 mg glucose.kg ideal body weight.min-1 continuous infusion of glucose with model assessment (CIGMA) test was used to quantitate glucose tolerance, beta cell function, and insulin sensitivity. Twenty-two Caucasian subjects who had impaired glucose tolerance identified on two separate tests underwent repeat testing after a median period of 24 months. At follow-up, 2 of the 22 subjects (9%) had Type 2 diabetes, 18 (82%) had impaired glucose tolerance, and 2 (9%) were normoglycaemic. The fasting and achieved (60-min) glucose levels were significantly higher at follow-up (mean +/- SD) (5.7 +/- 0.8 vs 5.5 +/- 0.5 mmol l-1, p = 0.029 and 10.0 +/- 0.9 vs 9.6 +/- 0.6 mmol l-1, p = 0.021, respectively), and beta cell function was significantly lower (median and interquartile range): 75% (50-93%) vs 90% (70-135%), p = 0.009. The changes in fasting plasma glucose were found to correlate with change in body mass index (rs = 0.46, p = 0.03). We conclude that impaired glucose tolerance is associated with decline in beta cell function, and denotes substantial risk of hyperglycaemic progression. Randomized controlled trials are warranted to determine whether exercise programmes, dietary advice, and attentive follow-up and effective preventive strategies for subjects with impaired glucose tolerance.

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations

To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). Comparative study of endocrinologic parameters in PCOS women. University Hospital Reproductive Endocrinology Unit. Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Comparative effects of quinine and quinidine on glucose metabolism in healthy volunteers.

1. To investigate the relative effects of quinine and quinidine on glucose metabolism, 11 healthy males aged 17-32 years were given three separate 1 h intravenous infusions; normal saline alone, quinine dihydrochloride 10 mg base kg-1 body weight (BW) in normal saline, and quinidine dihydrochloride 10 mg base kg-1 BW in normal saline. A constant infusion of 5 mg glucose kg-1 ideal BW min-1 was given for 1 h before and during each study. 2. Assessment of pancreatic beta cell function and tissue insulin sensitivity from plasma glucose and insulin concentrations at the end of the first hour using the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique confirmed normal glucose tolerance for each subject on each test day. 3. Plasma glucose concentrations at 1 h were similar to those at 2 h. There was no significant difference between the plasma glucose profiles during the three infusion regimes (P greater than 0.05). Plasma insulin rose significantly during the second hour (P less than 0.0001); increments after quinine (geometric mean [-1 s.d- +1 s.d.]; 47.0 [27.8-79.4] mu l-1) were significantly greater than those after quinidine (19.8 [6.1-65.2] mu l-1) and saline (7.5 [0-21.5] mu l-1; P less than 0.05). Plasma quinine concentrations at the end of the infusion (6.5 +/- 4.4 mg l-1) correlated with insulin increments during the second hour (r = 0.662, P = 0.028) and were significantly greater than those of quinidine (3.0 +/- 0.8 mg l-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)