Coffee, tea and diabetes: the role of weight loss and caffeine.

OBJECTIVE: To assess the effect of weight change on the relationship between coffee and tea consumption and diabetes risk. DESIGN: Prospective cohort study, using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow Up Study. Survival analyses were conducted using 301 selfreported cases of diabetes and eight documented diabetes deaths during an 8.4-y follow-up. SUBJECTS: A total of 7006 subjects aged 32-88 y with no reported history of diabetes were included in the study. RESULTS: For all subjects combined, increases in consumption of ground-caffeinated coffee and caffeine at baseline were followed by decreases in diabetes risk during follow-up. There were significant statistical interactions between age and consumption of caffeine (P=0.02) and ground-caffeinated coffee (P=0.03). Age-stratified analysis showed that the decrease in diabetes risk only applied to < or =60-y-old subjects, for whom the decrease in diabetes risk also obtained for ground-decaffeinated coffee and regular tea. The multivariate hazard ratio (HR) and 95% confidence interval for a 2 cups/day increment in the intake of ground-caffeinated coffee, ground-decaffeinated coffee and regular tea was 0.86 (0.75-0.99), 0.58 (0.34-0.99) and 0.77 (0.59-1.00), respectively. The diabetes risk was negatively related to the consumption in a dose-response manner. There were strong statistical interactions between prior weight change and beverage consumption for < or =60-y-old subjects. Further analysis revealed that the decrease in diabetes risk only applied to those who had lost weight, and that there was a positive dose-response relationship between diabetes risk and weight change. For example, the multivariate HR and 95% confidence interval for >0 vs 0 cups/day of ground-decaffeinated coffee was 0.17 (0.04-0.74), 0.52 (0.19-1.42), 0.77 (0.30-1.96) and 0.91 (0.39-2.14) for subgroups with weight change of < or =0, 0-10, 10-20 and >20 lbs, respectively. There was no significant association between diabetes risk and consumption of instant-caffeinated coffee, instant-decaffeinated coffee or herbal tea. Caffeine intake appeared to explain some, but not all, of the diabetes-risk reduction and weight change. CONCLUSION: The negative relationship between diabetes risk and consumption of ground coffee and regular tea, observed for all NHEFS subjects, actually only applied to nonelderly adults who had previously lost weight.

Miglitol (BAY m 1099) treatment of diabetic hypothalamic-dietary obese rats improves islet response to glucose.

OBJECTIVE: The well-absorbed alpha-glucosidase inhibitor, miglitol (BAY m 1099), was included in the diets of hypothalamic-dietary obese diabetic rats to investigate its ability to improve glycemia and thereby reverse glucotoxic effects on islet secretory response. RESEARCH METHODS AND PROCEDURES: Female rats received bilateral electrolytic lesions of the ventromedial hypothalamus and were fed high-fat, sucrose-supplemented diets until hyperinsulinemia and hyperglycemia were observed after 3 hours of food deprivation (nonfed). Diabetic animals were assigned to miglitol-treated (40 mg/100 g of diet) or untreated groups for 3 weeks; pancreatic islets were isolated for incubation experiments. RESULTS: No differences in food intake, body weights, or nonfed plasma glucose or insulin levels were seen between treated and untreated diabetic rats. Islets isolated from untreated diabetic rats showed elevated basal insulin release and no insulin secretory response to an elevation in glucose concentration. In contrast, islets obtained from miglitol-treated rats showed more normal basal release and a significant insulin secretory response to glucose. Incubation of islets, obtained from normal control rats or untreated diabetic rats, in media containing miglitol at levels estimated to exist in plasma of treated rats had no effect on islet insulin secretory responses to glucose. DISCUSSION: Islet secretory response was improved despite continued hyperglycemia and severe insulin resistance. Miglitol treatment may improve islet sensitivity to glucose either through effects on islet metabolism requiring prolonged exposure or by improvement in postmeal glycemia, despite persistent hyperglycemia.

Diabetic rats prefer glucose-paired flavors over fructose-paired flavors.

Prior studies indicate that glucose has a more potent postingestive reinforcing effect than fructose. The role of insulin in this effect was examined by comparing sugar-conditioned flavor preferences in normal and streptozotocin-diabetic rats. In Experiment 1, diabetic rats, like normal rats, preferred a cue flavor that had been mixed into 8% glucose solution over a flavor mixed with 8% fructose. Both taste and postingestive properties of glucose may have contributed to this preference. Experiment 2 evaluated postingestive reinforcement by pairing cue flavors with intragastric infusions of glucose and fructose. Both diabetics and normals acquired a preference for the flavor paired with intragastric 16% glucose infusions over the flavor paired with 16% fructose infusions although the preference was somewhat smaller in the diabetic rats. Taken together, the results indicate that a normal insulin secretory response to glucose is not required for glucose-conditioned flavor preference. The diabetic rats' reduced flavor preference in Experiment 2 suggests that insulin may play some role in glucose conditioning although this may be secondary to alterations in gastrointestinal motility characteristic of diabetic animals.

The VMH-dietary obese rat: a new model of non-insulin-dependent diabetes mellitus.

A model of non-insulin-dependent diabetes mellitus (NIDDM) has been developed in adult rats by combining bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) and high fat-high sucrose diets. VMH-dietary obese rats showed fasting hyperinsulinemia (> or = 540 pM) and hypertriglyceridemia (> or = 180 mg/dl) generally within 3 wk on the protocol. Fasting hyperglycemia (> or = 10 mM) was observed in the majority of animals in seven consecutive experiments. Hyperglycemic animals showed impaired glucose tolerance despite high prevailing insulin levels. Pancreatic islets isolated from VMH-dietary obese rats showed a loss of insulin secretory response to glucose by week 5, before the onset of hyperglycemia. Islets from hyperglycemic rats no longer responded to an increase in glucose concentration and failed to suppress insulin release normally in response to 15 nM norepinephrine or to a decrease in glucose concentration. This model mimics the major characteristics of obesity-associated human NIDDM as well as several stages of its progression, rendering it useful for studying the etiology of the metabolic and secretory defects in the syndrome.

Effect of milk ingestion on pulmonary function in healthy and asthmatic subjects.

Since Maimonides, it has been common in folk medicine to proscribe milk for asthmatics because its putative stimulation of mucus production can exacerbate asthma symptoms. A literature review, however, failed to reveal any data supporting this notion. We, therefore, compared the effects of ingesting 16 oz. of whole milk (16 g lipid), skim milk (2 g lipid), and water (each on a separate day) on: (1) forced expiratory volume in 1 second (FEV1), (2) forced expiratory flow at 50% of vital capacity (V50), and (3) pulmonary diffusing capacity (DLCO) in 11 asthmatic and 10 nonasthmatic subjects. Measurements were taken at 30 minute intervals for 3 hours. The two milk types did not significantly change FEV1 or V50 in either group, indicating that the amount ingested did not change airway resistance sufficiently to alter airflow parameters. In the asthmatic group, however, DLCO decreased progressively over the 3 hours by 6.8 +/- 1.4% (mean +/- SE) per hour after whole milk (maximum reduction = 21 +/- 1.4%) but not after water or skim milk. In the nonasthmatic group, no significant effects were observed on DLCO after any of the liquids. These data suggest that milk lipids can disturb gas exchange in asthmatic patients.

Role of Ca2+ in secretagogue-stimulated breakdown of phosphatidylinositol in rat pancreatic islets.

Breakdown of phosphatidylinositol (PI) has been shown to be increased during Ca2+-mediated stimulation of cellular responses in many systems and has been proposed to be involved in stimulus-secretion coupling. The effects on PI breakdown of insulin secretagogues that alter cellular Ca2+ or cyclic (c)AMP levels were investigated in perifused rat islets of Langerhans. Isolated islets were labeled with myo-[2-3H(N)]inositol and the efflux of 3H-labeled metabolites was monitored. Glucose (16.7 mM) greatly increased 3H release in a manner that paralleled the second phase of the insulin secretory response; by 60 min, the amount of [3H]PI in the islet decreased by 50%. Removal of Ca2+ from the perifusate or blockade of Ca2+ entry through the voltage-dependent channels by D600 (20 microM) abolished the glucose-induced increase in 3H efflux. Depolarization with 47 mM K+, which increases Ca2+ entry, stimulated protracted 3H and insulin release. Glucose-stimulated output of 3H was not prevented by epinephrine (1 microM) even though the insulin response was abolished. In contrast, 3H output was not affected by isobutylmethylxanthine (1 mM), known to raise cellular levels of cAMP, although insulin release was stimulated. These findings indicate that PI breakdown is not related to the exocytotic process since stimulation of insulin release and PI breakdown could be uncoupled, and that it is not associated with cAMP-mediated regulation of insulin release. PI breakdown in islets differs from the immediate, transient phenomenon reported in other systems in both its timing and requirement for Ca2+. It appears to result from the entry of Ca2+ and not to be the mechanism by which glucose initiates Ca2+ influx.

Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases.

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.

Long-term reversal of streptozotocin-induced diabetes in rats by intramuscular islet implantation.

The ability of pancreatic islets implanted into abdominal muscle to effect a recovery from streptozotocin-induced diabetes was compared with that of i.p implants. Pancreases from 17 to 35 Lewis neonates were cultured for 6 days and placed in i.m. or i.p. sites in severely diabetic Lewis rats. Body weight, food and water intakes, urinary output, and 4-hr fasted plasma glucose levels returned to normal in both groups. Neither plasma insulin and glucose responses to intravenous glucose tolerance tests nor plasma glucose responses to oral glucose tolerance tests differed among i.m. or i.p. implant recipients and normal, age-matched controls, even after 1 week's prior challenge of insulin secretory capacity by a high sucrose diet. Plasma glucose levels were reduced after oral administration of tolbutamide in the three groups. Plasma glucagon of i.m. and i.p. implant recipients after a 4-hr fast or after an oral load of arginine were not significantly different from those of controls, although levels tended to be higher in the implant groups. Neither i.m. nor i.p. implant groups reverted to the diabetic state in the 10 months following pancreatic implantation. These findings validate the long-term efficacy of intramuscular implantation of cultured islets in reversing diabetes in inbred rats.