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PubMed1993

Amplitude suppression of the pulsatile mode of immunoradiometric luteinizing hormone release in fasting-induced hypoandrogenemia in normal men.

In the male rodent and primate, fasting or severe caloric restriction significantly decreases serum testosterone concentrations, putatively via inducing secondary hypogonadotrophism. To clarify this presumptive pathophysiology, we have used: 1) a high sensitivity immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay of LH; 2) blood sampling every 5 min for 24 h basally and every 10 min for 3 h after GnRH injection before and after a 5-day (water only) fast in eight healthy young men; and 3) deconvolution analysis to evaluate in vivo LH secretory burst frequency, amplitude, duration, and mass, and LH half-life simultaneously. We documented a 50% fall in serum total and free testosterone concentrations, and a 30% decrease in 24-h mean serum LH concentrations (viz., fed 3.0 +/- 0.47 vs. fasted 2.1 +/- 0.39 U/L, P = 0.043). Deconvolution analysis revealed preservation of LH secretory pulse frequency (fed 12.9 +/- 0.48 vs. fasted 12.6 +/- 0.78 secretory bursts/day, P = NS) during fasting-induced hypogonadotropism. The duration of computer-resolved LH secretory bursts, the interburst interval, and the calculated endogenous half-life of LH also did not change, whereas LH secretory burst mass declined significantly; viz. from 28 +/- 5 in the fed to 14 +/- 3.2 U/L of distribution volume/day in the fasted state (P = 0.034). In contrast, LH release after a 10 micrograms pulse of GnRH iv was enhanced during fasting in seven of the eight men. Fasting also decreased mean (24 h) serum TSH and PRL, increased cortisol, dehydroepiandrosterone sulfate and GH, and did not affect FSH concentrations or the radioiodinated albumen distribution space. In summary, in young men 5 days of nutrient deprivation selectively attenuates the mass of LH secreted per burst without altering LH secretory event frequency or LH half-life. We infer that decreased LH release per burst is due to decreased hypothalamic GnRH impulse strength, since LH release induced by a submaximally effective pulse of exogenous GnRH is amplified rather than attenuated.

Adult↗
PubMed1995

Short-term fasting affects luteinizing hormone secretory dynamics but not reproductive function in normal-weight sedentary women.

Acute food withdrawal reversibly inhibits the hypothalamic-pituitary-gonadal axis in men and in rhesus monkeys, and it produces defects in LH pulsatility in normal-weight women. However, the clinical effect of short-term nutritional deprivation on the reproductive axis of normally cycling women has not been evaluated. Thus we studied the effect of a 3-day fast during the midfollicular phase on menstrual cycle length, gonadotropin secretory patterns, follicular development, and ovulation. After a baseline ovulatory cycle, 12 women within 15% of ideal body weight were randomized to be fed (n = 7) or fasted (n = 10) on cycle days 7 to 9. Five of the women repeated the study and received the alternate diet. Endocrine and metabolic parameters of fasting and reproductive physiology were measured on cycle days 6 to 12. Fasted physiology was demonstrated by characteristic alterations in growth hormone, insulin-like growth factor I, TSH, and T3 levels. During fed cycles, the number of LH pulses remained constant on cycle days 6, 9 and 11, whereas mean LH levels, LH area under the curve, and LH pulse amplitude increased significantly over this time (all P < 0.05). In contrast, fasted cycles were marked by a significant decrease in the number of LH pulses on the last day of the fast (cycle day 9, P < 0.05) and by a lack of increase over time of mean LH values, LH area under the curve, and LH pulse amplitude. Follicle development, as assessed by daily ultrasound examination and estradiol measurements, was similar in all cycles and was followed by ovulation in all women; follicular and luteal phase lengths of fasted and fed cycles were similar. We conclude that the alterations in LH secretory dynamics that occur during a 3-day fast are not sufficient to perturb follicle development and cycle lengths in normal-weight sedentary women. The resilience of the reproductive axis in these healthy women contrasts with the sensitivity of the hypothalamic-pituitary-gonadal axis to acute nutritional withdrawal in men and in monkeys. We speculate that differences in the set point for sensing fuel availability or in the status of energy balance before the initiation of food deprivation may account for these species-specific and sex-specific variabilities.

Adult↗
PubMed1996

Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men--a clinical research center study.

In healthy subjects, short term fasting suppresses the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum levels of TSH and LH. However, effects of fasting on pulsatile release of TSH, LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each underwent two 2-day studies: a baseline study during normal caloric intake and a fasting study during 56 h of caloric deprivation. During the final 24 h of each study, blood samples were drawn every 15 min for measurement of serum TSH, LH, FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50% suppression of mean TSH levels and TSH pulse amplitude, without altering TSH pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH levels only decreased by 13%, without changes in FSH pulse parameters, whereas mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show that short term fasting has a greater suppressive effect on the hypothalamic-pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more resistant to fasting-induced suppression than LH, implying discordant regulation of the two gonadotropins during nutritional deprivation. alpha-Subunit suppression during fasting appears to parallel that seen for LH.

Adult↗
PubMed1996

Effect of short-term fasting on free/dissociable insulin-like growth factor I concentrations in normal human serum.

A small portion of circulating insulin-like growth factor I (IGF-I) is detected in the free or readily dissociable state, which is thought to be the metabolically active form. The amount of free/dissociable IGF-I in serum is dependent on a complex interplay between the production rate and the concentrations of IGF-I and IGF-binding proteins (IGFBPs). IGF availability is also influenced by posttranslational changes in IGFBPs that affect the affinity of IGFBPs for IGF-I. In the present study, we examined whether a short term fast (approximately 12 h) alters the serum concentration of free/dissociable IGF-I, and whether these changes are associated with alterations in IGFBP-1 and the proteolysis status of IGFBP-3. Circulating free/dissociable IGF-I concentrations, as assessed by a two-site immunoradiometric assay, did not differ between fasting and 4 h after a morning meal (1.48 +/- 0.07 vs. 1.50 +/- 0.07 microgram/L, respectively). Likewise, free/dissociable IGF-I levels measured by RIA after separation by centrifugal ultrafiltration were not different between the two groups (1.43 +/- 0.14 vs. 1.38 +/- 0.18 microgram/L, respectively). IGF-I bioactivity, as measured by thymidine incorporation by fibroblasts, did not differ in fasting and 4-h postprandial sera. There was no difference in IGFBP-3 and total acid-ethanol-extractable IGF-I concentrations in serum from fasted and fed subjects. In contrast, the concentration of IGFBP-1 in the serum was increased approximately 5-fold in the fasted state compared to fed values. IGFBP-1 existed in a highly phosphorylated form under fasting conditions. There was no change in IGFBP-3 proteolysis assessed either in vivo or in vitro between the fasting and fed states. The results indicate that a physiologically relevant short term overnight fast does not alter the circulating levels of free/dissociable IGF-I despite a marked elevation in IGFBP-1.

Adult↗
PubMed2003

A liberalized fasting guideline for formula-fed infants does not increase average gastric fluid volume before elective surgery.

UNLABELLED: Recommended preoperative fasting intervals for infant formula vary from 4 to 8 h. We conducted a prospective, randomized, observer-blinded trial of 97 ASA physical status I and II infants scheduled for elective surgery to determine whether average gastric fluid volume (GFV) recovered from infants formula-fasted for 4 h (liberalized fast, Group L) differed from that recovered from infants allowed clear liquids up until 2 h, but fasted 8 h for formula and solids (traditional fast, Group T). In Group L, 31 of 39 subjects followed protocol and ingested formula 4-6 h before surgery. In Group T, 36 of 58 subjects followed protocol, taking clear liquids 2-5 h before the induction of anesthesia. Thirty subjects had prolonged fasts and were included only in a secondary intent-to-treat analysis. Respective mean age (5.7 +/- 2.3 versus 6.4 +/- 2.4 mo; range, 0.7-10.5 mo), weight (7.5 +/- 1.8 versus 7.5 +/- 1.1 kg), and volume of last feed (4.9 +/- 2.2 versus 4.0 +/- 2.3 oz.) did not vary between Groups L and T. GFV (L: 0.19 +/- 0.38 versus T: 0.16 +/- 0.30 mL/kg) and gastric fluid pH (L: 2.5 +/- 0.5 versus T: 2.9 +/- 1.3) did not vary. For all subjects, GFV (mL/kg) increased with age (Spearman correlation coefficient = +0.23, P = 0.03). Infant irritability and hunger and parent satisfaction were similar between groups. We conclude that average GFV after either a 4- to 6-h fast for infant formula or 2-h fast after clear liquids is small and not significantly different between groups. On the basis of these findings, clinicians may consider liberalizing formula feedings to 4 h before surgery in selected infants. IMPLICATIONS: Healthy infants aged < or =10.5 mo may drink formula up to 4 h before surgery without increasing gastric fluid volume compared with infants allowed clear liquids up to 2 h and formula 8 h before surgery.

Affect↗
PubMed2005

Glucose production and substrate cycle activity in a fasting adapted animal, the northern elephant seal.

During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose cycle activity were investigated. Glucose cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80+/-0.65 mg kg(-1) min(-1) early and 2.21+/-0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast (t=5.27, 2.84; P=0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.

Animals↗
PubMed1976

[Effects of fasting on the renal function of rats: Clearance experiments and Henle's loop microperfusion].

Results of a previous experiment indicated that osmotic pressure and sodium concentration in distal tubular fluid of the nephron constantly microperfused were increased during natriuresis of fasting rats. The present experiments were performed in order to clarify whether or not water reabsorption and urea movement in Henle's loop, which may modify osmotic pressure and sodium concentration in distal fluid, change in the fasting rat kidney. Non-fasting, 18 approximately 24 hours and 4 approximately 5 days-fasting rats were used. After surgical procedures, the animal was infused with 2% saline at 33.3 mul/min. The loop of Henle was perfused with 1% saline containing 0.05% lissamine green, 3H-inulin and 14C-urea at 29.1 nl/min. In the fasting groups, urinary flow and sodium excretion were increased, whereas urea excretion was depressed and inulin clearance showed a tendency to decrease. Tubular fluid to plasma ratio of osmotic pressure in the distal tubule was elevated without change of water reabsorption. From present and previous results, the increases of osmotic pressure and sodium concentration in distal tubular fluid of fasted rat kidney cannot be explained from an increase of water reabsorption in the Henle's loop. Consequently, natriuresis with fasting may contribute partially to an inhibition of sodium reabsorption in Henle's loops, possibly in the thick ascending limbs. Recovery of C-urea perfused into Henle's loops of fasted rats increased.

Animals↗
PubMedDate not supplied

Effects of seasonality and fasting on the body mass and plasma growth hormone concentrations of the raccoon dog (Nyctereutes procyonoides) and the blue fox (Alopex lagopus).

Growth hormone (GH) promotes growth and endochondral ossification, but it is also important in the response to fasting due to its effects of increasing gluconeogenesis and lipolysis. In this study eleven raccoon dogs and blue foxes were followed for six months and their body mass and GH levels were measured. In November half of the animals of both species were put to a three-week fast. There were no significant differences in the GH levels between the animals of different ages and the subadults and adults both had quite low GH levels in the summer. Fasting had no effect on the GH levels of the raccoon dogs, but the fasting blue foxes had lower GH concentrations than the controls in Nov 16th. The control blue foxes experienced a significant increase in the GH levels in early November and the fasting blue foxes in late November. The GH concentrations of all the raccoon dogs rose in early December. As fasting did not cause an elevation in the GH levels but the concentrations increased with decreasing temperature and shortening daylength, the autumnal GH secretion of these species could be regulated by endogenous seasonal rhythms entrained by exogenous Zeitgebers such as temperature or photoperiod. The autumnal increase of GH levels contributes to the response to fasting as an adaptation to survive the winter months with inadequate nutrition. The raccoon dog which spends the coldest part of the winter in winter sleep seems to be better adapted to a total fast than the actively wintering blue fox.

Animals↗
PubMed1994

Influence of prolonged fasting on thyroid hormone modulation of lipolysis in isolated epididymal adipocytes of Wistar rats.

Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 degrees C and then fasted for 3 days, with or without daily intraperitoneal injection of 3,5,3'-triiodo-L-thyronine (4.6 nmol T3/100 g body weight). Age-matched fed euthyroid rats were used as controls. All the experiments were carried out using isolated epididymal adipocytes. Basal lipolysis was higher during fasting in euthyroid or T3-treated adipocytes than in hypothyroid adipocytes. Adipocytes of fed hypothyroid rats were quite unresponsive to theophylline alone or combined with adrenaline or isoproterenol, whereas lipolysis was stimulated by these drugs in euthyroid or T3-treated adipocytes. Such a stimulated lipolysis was increased partially by fasting in hypothyroid adipocytes and was restored to a euthyroid level in T3-treated adipocytes. Lipolysis was more stimulated by adenosine deaminase in fasted euthyroid adipocytes than in fed ones. Hypothyroid and T3-treated adipocytes were unresponsive to adenosine deaminase except in fasted T3-treated rats. In these adipocytes, lipolysis was activated by the combination of adenosine deaminase plus theophylline. Finally, lipolysis was inhibited strongly in hypothyroidism while it was activated weakly by fasting. Lipolysis was inhibited slightly in fasted hypothyroid rats and thyroid hormone restored lipolysis. The findings are discussed in terms of the dual regulation of lipolysis by fasting and thyroid hormones.

Adenosine Deaminase↗
PubMed2001

Orexin-A and leptin change inversely in fasting non-obese subjects.

OBJECTIVE: Leptin, neuropeptide-Y (NPY) and orexin are peptides regulating energy metabolism and appetite control. NPY and orexin are mainly found in the central nervous system and they have also recently been found in the peripheral nervous system. We investigated how fasting affects changes in circulating concentrations of these peptides and their association with nutritional and metabolic parameters in humans. DESIGN AND METHODS: Ten non-obese female patients with psychosomatic disorders fasted for 7 or 10 days. Blood samples were collected at 0800 h before fasting, on the 3rd and 7th days during the fast (with an additional sample taken on the 10th day when the fasting continued for 10 days) and on the 3rd and 7th days of refeeding. We measured blood concentrations of orexin-A, NPY, leptin, adrenocorticotropin, cortisol, insulin, C-peptide, glucose, and beta-hydroxybutyrate. RESULTS: Body mass index and plasma leptin concentrations concomitantly and significantly decreased during fasting, whereas serum orexin-A concentrations significantly increased and were negatively correlated with plasma leptin concentrations. Plasma NPY concentrations decreased slightly but were not significantly different from the prefasting values, and no significant relationship with leptin or orexin-A was found. Orexin-A and leptin concentrations showed a significant inverse correlation with serum glucose, insulin, C-peptide, and beta-hydroxybutyrate concentrations. Only changes in plasma leptin concentrations showed a significant negative correlation with serum cortisol concentrations. All the measured indices which changed during fasting returned to the prefasting concentrations by the 7th day of refeeding. CONCLUSION: Peripheral orexin-A and leptin concentrations inversely change during fasting, which is significantly correlated with energy metabolism in humans.

Adolescent↗
PubMed1980

In-vivo and in-vitro studies on the effects of maternal fasting during embryonic organogenesis in the rat.

Pregnant rats were fasted for periods of 6, 12, 24 or 36 h terminating at 10 1/2 days post coitum (p.c.); virgin rats were fasted concurrently. Both groups showed similar loss of body weight and fall in serum glucose levels. Embryos from rats which were fasted for 12 h or longer showed retarded growth and differentiation compared with embryos from non-fasted animals. Another group of rats, similarly fasted for periods before 10 1/2 days p.c. were then fed ad libitum until 15 1/2 days p.c.; the fetuses were smaller than fetuses of similar age from non-fasted rats. Embryos from fed mothers were explanted at 9 1/2 days p.c. and cultured for 45 h in rat serum prepared from fed or fasted animals. Embryonic development was retarded in the serum from fasted rats unless glucose was added to raise the glucose level to that of normal serum.

Animals↗
PubMed2006

Diabetes and impaired fasting glucose as predictors of morbidity and mortality in male coronary artery disease patients with reduced left ventricular function.

OBJECTIVES: To evaluate the prognostic value of impaired fasting glucose and diabetes mellitus in male patients with coronary artery disease and poor left ventricular function. METHODS AND RESULTS: From a prospective database on patients referred for gated myocardial perfusion imaging between 1998 and 2002 all male patients with a history of coronary artery disease and poor left ventricular function were selected. Poor function was defined as left ventricular ejection fraction < or = 40%. Subjects were classified as non-diabetics with fasting blood glucose levels < 110 mg/dL, non-diabetics with impaired fasting glucose (fasting blood glucose between 110 and 125 mg/dL) and diabetics. Median follow-up was 2.7years. End points were all-cause mortality, cardiac death and hospitalization for heart failure. One hundred and sixty patients were selected (age 65 +/- 9 years and left ventricular ejection fraction 29 +/- 8%). In univariate analysis atrial fibrillation, NYHA class, glycaemia and diabetes mellitus discriminated between survivors and non-survivors. In Cox multivariate regression analysis for all-cause mortality only NYHA class and diabetes mellitus remained significant. Kaplan Meier analysis showed that diabetics had the worst survival and non-diabetics with glucose < 110 mg/dL had the best survival. Non-diabetics with impaired fasting glucose had intermediate survival. Analysis for cardiac death/hospitalization for heart failure showed similar results. CONCLUSION: In male patients with coronary artery disease and impaired left ventricular function diabetes mellitus and fasting glucose are strongly predictive of poor outcome. Diabetics have the worst prognosis but non-diabetics with impaired fasting glucose also are at higher risk compared to nondiabetics with low fasting blood glucose.

Aged↗
PubMed1983

Effect of glucose stimulation on 45calcium uptake and total calcium content of pancreatic islets of fed and fasted rats and obese hyperglycemic mice.

Effects of fasting on glucose-induced changes of various calcium parameters were investigated. The total calcium content of islets of fed rats and obese mice, determined by fluorometric microanalysis, amounted to 575 +/- 25 and 600 +/- 75 pmol/microgram DNA, respectively. Fasting for 24 or 72 h had no effect on the calcium content of rat islets, but increased that of mice by 30%. Glucose stimulation did not alter their total calcium content. The amount of 45Ca (as percentage of total islet calcium content) taken up over 30 min by fed mouse islets at 2.5, 10, and 15 mM glucose was equivalent to 32%, 41%, and 44% and by fed rat islets to 25%, 31%, and 34%, respectively. The net uptake of fed rat islets over 60 min at 2.5 and 15 mM glucose amounted to 36% and 61%. Fasting for 24 h inhibited insulin secretion over 30 min but not 45Ca uptake, whereas both parameters were inhibited after fasting for 72 h. Insulin secretion of mouse islets, was inhibited after 24 and 72 h of fasting, but 45Ca uptake was not significantly affected. Since glucose stimulates 45Ca uptake without changing the total islet calcium content, it must represent 45Ca- 40Ca exchange. Stimulation of insulin secretion of rat islets is associated with an increased calcium influx rate and increased exchangeable calcium pool(s) size. Calcium pool(s) size seems not to be altered by 24 h of fasting; however, 72 h of fasting tends to decrease the pool(s) size. The inhibition of insulin secretion induced by 24 h of fasting is not due to an altered calcium uptake, but it may be due to a modification of intracellular handling of calcium.

Animals↗
PubMed1998

Increased levels of free fatty acids in fasted mice stimulate in vivo beta-cell electrical activity.

The electrical activity of pancreatic beta-cells in 48-h fasted mice has been recorded in vivo. Their electrical activity is exceedingly high at low levels of blood glucose when compared with control animals. For example, at a blood glucose concentration of 4.5 mmol/l, at which beta-cells are permanently hyperpolarized in control animals, fasted animals show continuous spiking activity. In fasted animals, hyperpolarization only occurs at glycemias below 2.2 mmol/l. As in fed animals, the electrical activity in fasted mice can be decreased or suppressed by the injection of diazoxide, indicating the participation of K(ATP) channels. The treatment of fasted animals with nicotinic acid, an inhibitor of lipolysis, produces a decrease in the levels of free fatty acids (FFAs) and a decrease in electrical activity, thereby restoring the dose-response curve for glucose in fasted animals to values close to those found in fed animals. Conversely, the injection of palmitic acid produces an increase in electrical activity without a change in blood glucose. These results point to FFAs as important regulators of electrical activity during fasting in vivo. They also indicate a dissociation of electrical activity and insulin release in fasted animals, since an increase in electrical activity is not associated with increased insulin secretion.

Animals↗
PubMed1997

A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: To determine the association of coronary heart disease (CHD) incidence with diabetes, fasting serum glucose, and insulin in a biracial cohort of middle-aged men and women. RESEARCH DESIGN AND METHODS: We examined a population-based sample (n = 13,446 free of baseline CHD) from four U.S. communities in 1987-1989. We defined diabetes on the basis of baseline fasting glucose concentration (> or = 7.8 mmol/l), medical history, and current medications. A central laboratory measured fasting insulin with a nonspecific radioimmunoassay. After 4-7 years, 209 men and 96 women developed CHD. RESULTS: After adjustment for sociodemographic characteristics, smoking status, ethanol intake, sports participation, and hormone replacement therapy, the relative risk of CHD for people with diabetes versus those without diabetes was 3.45 (95% CI 2.16-5.50) among women and 2.52 (1.78-3.56) among men. Relative risks of CHD with diabetes were somewhat lower in blacks than non-blacks, but because diabetes was more than twice as prevalent in blacks, the percentage of CHD cases attributable to diabetes (population attributable risk) was 27% for black women, 15% for non-black women, 8% for black men, and 12% for non-black men. Among people without diabetes, fasting glucose was not independently associated with CHD incidence. Among women without diabetes, there was a positive association between fasting insulin and CHD; multivariable adjusted relative risks of CHD across quintiles of fasting insulin were 1.00, 0.76, 2.08, 2.08 and 2.82 (P for linear trend = 0.02). However, among men without diabetes, fasting insulin and CHD were not associated. CONCLUSIONS: Diabetes conveys a high risk of CHD in black and non-black middle-aged men and women. Fasting insulin, however, is a CHD risk factor only among women in this cohort.

Black or African American↗
PubMed1998

Diabetes in urban African-Americans. VI. Utility of fasting or random glucose in identifying poor glycemic control.

OBJECTIVE: African-Americans have an increased prevalence of both diabetes and diabetes complications, creating an imperative for improved metabolic control. Because American Diabetes Association guidelines recommend that action be taken when HbA1c is > 8.0%, but access to rapid-turnaround HbA1c assays remains limited, we tested the utility of fasting and random plasma glucose cutoffs as indicators of HbA1c > 8.0%. RESEARCH DESIGN AND METHODS: Using receiver operating characteristics (ROC) analysis, we evaluated the sensitivity, specificity, and predictive value of fasting and random plasma glucose measurements in identifying an HbA1c > 8.0% (fasting n = 974, random n = 552). The population studied was predominantly African-American, middle-aged, and non-insulin-dependent. RESULTS: Fasting plasma glucose was a significant indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.87, 0.90, 0.87, and 0.84, respectively (all P < 0.0001). A fasting plasma glucose cutoff of > 9.2 mmol/l (165 mg/dl) provided a sensitivity of 80% and a specificity of 83% for the whole group and a 77% positive predictive value. Random plasma glucose was also a good indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.85, 0.91, 0.85, and 0.77, respectively (all P < 0.0001). A cutoff > 9.8 mmol/l (177 mg/dl) provided a sensitivity of 78% and a specificity of 77% for the whole group and a 78% positive predictive value. Overall, a plasma glucose > 11.1 mmol/l (200 mg/dl) identified an HbA1c > 8.0% with a predictive value of approximately 90% if done while fasting and a predictive value of approximately 80-85% if random. The utility of both fasting and random plasma glucose cutoffs was subsequently confirmed in a prospective study of another 2,309 and 1,396 patients, respectively. CONCLUSIONS: Although glucose levels cannot replace HbA1c determinations, measurement of fasting or random plasma glucose may be used during a clinic visit to identify poorly controlled type 2 patients with reasonable certainty and allow timely patient education and therapeutic intervention.

Black or African American↗
PubMed1999

Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.

OBJECTIVE: The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM. RESEARCH DESIGN AND METHODS: We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects. RESULTS: In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy. CONCLUSIONS: The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.

Administration, Oral↗
PubMed1999

Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men.

OBJECTIVE: Because of the available conflicting epidemiological data, we investigated the possible impact of fasting blood glucose as a risk factor for cardiovascular death in nondiabetic men. This study reports the results from a 22-year prospective study on fasting blood glucose as a predictor of cardiovascular death. RESEARCH DESIGN AND METHODS: Of the 1,998 apparently healthy nondiabetic men (aged 40-59 years), a total of 1,973 with fasting blood glucose < 110 mg/dl were included in the study in which also a number of conventional risk factors were measured at baseline. RESULTS: After 22 years of follow-up, 483 men had died, 53% from cardiovascular diseases. After dividing men into quartiles of fasting blood glucose level, it was found that men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. Even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness (Cox model), the relative risk of cardiovascular death for men with fasting blood glucose > 85 mg/dl remained 1.4 (95% CI 1.04-1.8). Noncardiovascular deaths were unrelated to fasting blood glucose level. CONCLUSIONS: Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.

Adult↗