The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 ± 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in body weight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities.

/pdf/the-natural-history-of-insulin-secretory-dysfunction-and-y82ked0pmy.pdf

The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus.

https://foodaddictionsummit.org/documents/StressEatingandtheRewardSystem.pdf

Stress, eating and the reward system

▪ Abstract Obesity is now recognized as a serious chronic disease, but there is pessimism about how successful treatment can be. A general perception is that almost no one succeeds in long-term maintenance of weight loss. To define long-term weight loss success, we need an accepted definition. We propose defining successful long-term weight loss maintenance as intentionally losing at least 10% of initial body weight and keeping it off for at least 1 year. According to this definition, the picture is much more optimistic, with perhaps greater than 20% of overweight/obese persons able to achieve success. We found that in the National Weight Control Registry, successful long-term weight loss maintainers (average weight loss of 30 kg for an average of 5.5 years) share common behavioral strategies, including eating a diet low in fat, frequent self-monitoring of body weight and food intake, and high levels of regular physical activity. Weight loss maintenance may get easier over time. Once these successful main...

Successful weight loss maintenance

Historically, nutrition principles and recommendations for diabetes and related complications have been based on scientific evidence and diabetes knowledge when available and, when evidence was not available, on clinical experience and expert consensus. Often it has been difficult to discern the level of evidence used to construct the nutrition principles and recommendations. Furthermore, in clinical practice, many nutrition recommendations that have no scientific supporting evidence have been and are still being given to individuals with diabetes. To address these problems and to incorporate the research done in the past 8 years, this 2002 technical review provides principles and recommendations classified according to the level of evidence available. It reviews the evidence from randomized, controlled trials; cohort and case-controlled studies; and observational studies, which can also provide valuable evidence (1,2), and takes into account the number of studies that have provided consistent outcomes of support. In this review, nutrition principles are graded into four categories based on the available evidence: those with strong supporting evidence, those with some supporting evidence, those with limited supporting evidence and those based on expert consensus.

Evidence-based nutrition recommendations attempt to translate research data and clinically applicable evidence into nutrition care. However, the best available evidence must still be moderated by individual circumstances and preferences. The goal of evidence-based recommendations is to improve the quality of clinical judgments and facilitate cost-effective care by increasing the awareness of clinicians and patients with diabetes of the evidence supporting nutrition services and the strength of that evidence, both in quality and quantity.

Before 1994, the American Diabetes Association’s (ADA’s) nutrition principles and recommendations attempted to define an “ideal” nutrition prescription that would apply to everyone with diabetes (3,4,5). Although individualization was a major principle of all recommendations, it was usually done within defined …

/pdf/evidence-based-nutrition-principles-and-recommendations-for-219364socu.pdf

Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications

'Stress' embraces the reaction to a multitude of poorly defined factors that disturb homeostasis or allostasis. In this overview, the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system have been utilized as objective measurements of stress reactions. Although long-term activation of the sympathetic nervous system is followed by primary hypertension, consequences of similar activation of the HPA axis have not been clearly defined. The focus of this overview is to examine whether or not repeated activation of these two stress centres may be involved in the pathogenesis of abdominal obesity and its comorbidities. In population studies adrenal hormones show strong statistical associations to centralization of body fat as well as to obesity. There is considerable evidence from clinical to cellular and molecular studies that elevated cortisol, particularly when combined with secondary inhibition of sex steroids and growth hormone secretions, is causing accumulation of fat in visceral adipose tissues as well as metabolic abnormalities (The Metabolic Syndrome). Hypertension is probably due to a parallel activation of the central sympathetic nervous system. Depression and 'the small baby syndrome' as well as stress exposure in men and non-human primates are followed with time by similar central and peripheral abnormalities. Glucocorticoid exposure is also followed by increased food intake and 'leptin resistant' obesity, perhaps disrupting the balance between leptin and neuropeptide Y to the advantage of the latter. The consequence might be 'stress-eating', which, however, is a poorly defined entity. Factors activating the stress centres in humans include psychosocial and socioeconomic handicaps, depressive and anxiety traits, alcohol and smoking, with some differences in profile between personalities and genders. Polymorphisms have been defined in several genes associated with the cascade of events along the stress axes. Based on this evidence it is suggested that environmental, perinatal and genetic factors induce neuroendocrine perturbations followed by abdominal obesity with its associated comorbidities.

Do stress reactions cause abdominal obesity and comorbidities

The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.

Effects of glucocorticoids on energy metabolism and food intake in humans

Energy metabolism in weight-stable postobese individuals.

Thermic effect of food in humans: methods and results from use of a respiratory chamber.

Differences in sleeping metabolic rate (SMR) among subjects may be related to different levels of energy expenditure associated with sleep stages. The relationship between energy expenditure and sleep stages was investigated overnight in 29 subjects (14 Caucasians and 15 Pima Indians, 18 males and 11 females; mean +/- SD, 31 +/- 7 yr, 83 +/- 26 kg, 27 +/- 11% fat). Sleep stages were determined by electroencephalogram recording, whereas energy expenditure was measured in a 1,000-liter Plexiglas sleep box constructed around a bed as a fast-response open-circuit indirect calorimeter. Eighty-five percent of the interindividual variability in SMR was explained by differences in fat-free mass, fat mass, age, sex, and race (r2 = 0.85). The intra-individual variance in SMR over time was related to sleep stages and to clock time. Within subjects, SMR in stage 3 was significantly lower than in stage 2 (-39 +/- 18 kcal/day; P < 0.05) and rapid eye movement sleep (-51 +/- 23 kcal/day; P < 0.05). Also, sleep stages were associated with different respiratory quotients. Because sleep stages are associated with only small differences in energy metabolism, our results suggest that sleep stages play a minor role in the variance of SMR among subjects. However, the duration of sleep may contribute to the variability of 24-h energy expenditure.

Relationship between sleep stages and metabolic rate in humans

A low body temperature is associated with a low metabolic rate for a given body size and body composition. These two traits might have been assets in the history of a population subjected to cycles of feast and famine, but became part of an obesity-prone syndrome in our westernized society characterized by plenty of food and a sedentary lifestyle. We tested whether Pima Indians have lower body temperatures than Caucasians, a trait which might partly explain the high prevalence of obesity in this population. Twenty-five Pima Indian (28 +/- 6 yrs, 87.8 +/- 22.8 kg, 29 +/- 9% body fat) and 25 Caucasian (30 +/- 5 yrs, 80.7 +/- 18.4 kg, 22 +/- 11% body fat) men had body core temperatures measured by telemetry for 24 h while in a respiratory chamber. Mean daily body core temperature was 36.93 +/- 0.12 and 36.90 +/- 0.22 degrees C in Pima Indians and Caucasians, respectively. Since body core temperature during sleep (SLBCT) correlated with percentage body fat, a subset of 10 Pima Indians and 10 Caucasians were pair-matched for body weight and percentage body fat. In this group, SLBCT was lower in Pima Indians than in Caucasians (36.45 +/- 0.10 vs 36.65 +/- 0.27 degrees C; P < 0.01) and, ethnic group accounted for 20% of the variance in SLBCT (P < 0.01). Surprisingly, the lower SLBCT was not associated with a low metabolic rate and therefore does not seem to play a role in the etiology of obesity in Pima Indians.(ABSTRACT TRUNCATED AT 250 WORDS)

D E Larson

Papers

Effects of glucocorticoids on energy metabolism and food intake in humans

Energy metabolism in weight-stable postobese individuals.

Thermic effect of food in humans: methods and results from use of a respiratory chamber.

Relationship between sleep stages and metabolic rate in humans

Racial difference in body core temperature between Pima Indian and Caucasian men.