Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study.

Background: Obesity is common in type 2 diabetes (T2DM) and is associated with increased risk of morbidity and all-cause mortality. This analysis describes weight changes associated with insulin detemir initiation in real-life clinical practice.

Methods: Study of Once-Daily Levemir (SOLVE) was a 24-week international observational study of once-daily insulin detemir as add-on therapy in patients with T2DM receiving oral hypoglycaemic agents (OHAs).

Insulin resistance of protein metabolism in type 2 diabetes and impact on dietary needs: a review.

Evidence shows that the metabolism of protein is altered in type 2 diabetes mellitus and insulin resistance not only applies to glucose and lipid but protein metabolism as well. Population surveys report greater susceptibility to loss of lean tissue and muscle strength with aging in diabetes. Prevention of sarcopenia requires that protein receives more attention in dietary prescriptions.

Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia.

Background & Aims: Insulin resistance of protein anabolism has been speculated to underlie the skeletal muscle wasting characteristic of cancer cachexia. We tested whether insulin resistance is present in cachectic lung cancer patients and if a sustained, physiological elevation of amino acids with hyperinsulinemia would compensate for it.

Methods: Whole-body [(13)C]leucine and [(3)H]glucose kinetics were assessed in 10 male non-small cell lung cancer (NSCLC) patients and 10 healthy matched controls during a euglycemic, hyperinsulinemic clamp under conditions of isoaminoacidemia followed by hyperaminoacidemia.

Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus.

Aims/hypothesis: Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to it in type 2 diabetes. However, the effect of hyperaminoacidaemia on glucose disposal in type 2 diabetic individuals remains to be determined.

Protein anabolic responses to a fed steady state in healthy aging.

Background: Protein anabolism in response to feeding may be impaired with aging. To determine if this could contribute to muscle loss, we studied fed-state metabolic responses in healthy, non-sarcopenic elderly women.

Methods: Whole-body [(3)H]glucose and protein ([(13)C]leucine) kinetics were measured, and muscle protein fractional synthesis rate ([(2)H(5)]phenylalanine) and signaling events were assessed from vastus lateralis biopsies in eight elderly (73 ± 3 years) and eight young women (24 ± 1 years), using a simulated fed steady-state clamp.

Postprandial insulin sensitivity and thermogenesis in frail elderly women.

The frailty syndrome is associated with inflammation, hypercortisolemia, and cardiovascular diseases, all of which are linked with insulin resistance. But whether frailty is characterized by insulin resistance is unclear, especially in the postprandial state. The prevalence of underweight with frailty is high.

Glycerol-induced hyperhydration: a method for estimating the optimal load of fluid to be ingested before exercise to maximize endurance performance.

Glycerol-induced hyperhydration (GIH) has been shown to increase endurance performance (EP). However, EP starts declining at a dehydration level >2% body weight (BW). It thus appears that the use of GIH is only required when athletes anticipate that their fluid intake during exercise would not be sufficient to prevent a loss of BW >2%.

Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat.

Whether frail elderly subjects are more insulin resistant (IR) than non-frail is unclear. How obesity, muscle mass, inflammation, hormonal and lipid status, oxidative stress, antioxidant capacity and physical activity influences insulin sensitivity (IS) in frail elderly subjects remains uncertain. We determined (1) whether frail elderly persons are more IR than non-frail elderly and (2) the influence of abdominal fat mass (AFM), muscle mass index (MMI), inflammation (CRP), hormonal (cortisol, free IGF-1, DHEA) and lipid (FFA, triglyceride (TG)) status, oxidative stress (paraoxonase-1 (PON-1), malondialdehyde (MDA)), antioxidant capacity (vitamin C, E) and physical activity (PASE questionnaire) on IS (QUICKI) in 16 frail obese (FO), 17 frail lean (FL) and 21 healthy, non-obese (HN) elderly subjects.

A meta-analysis of the effects of glycerol-induced hyperhydration on fluid retention and endurance performance.

The authors determined, through a meta-analytic approach, whether glycerol-induced hyperhydration (GIH) enhances fluid retention and increases endurance performance (EP) significantly more than water-induced hyperhydration (WIH). Collectively, studies administered 23.9 +/- 2.

Insulin resistance of protein metabolism in type 2 diabetes.

Objective: We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it.

Research Design And Methods: Hyperinsulinemic ( approximately 570 pmol/l), euglycemic (5.

Determinants of whole-body protein metabolism in subjects with and without type 2 diabetes.

Objective: Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes and obesity. We hypothesized that glycemia, insulin resistance, and waist circumference modulate these alterations in type 2 diabetes and, to a lesser extent, in individuals without type 2 diabetes.

Research Design And Methods: In 88 lean and obese subjects without and 40 with type 2 diabetes on an inpatient protein-controlled isoenergetic diet for 7 days, whole-body protein turnover was measured using the fed-fasted 60-h oral (15)N-glycine method.

Protein turnover and requirements in the healthy and frail elderly.

There are as yet no definitive data that warrant the establishment of evidence-based dietary protein recommendations for the elderly. We reviewed the relevance of the new 2002 recommended protein intake of 0.80 g/kg body weight.

Influence of adiposity in the blunted whole-body protein anabolic response to insulin with aging.

Background: Although insulin resistance of glucose is often reported with aging, that of protein metabolism is still debated. We tested if the insulin sensitivity of protein metabolism parallels that of glucose and is altered with aging.

Methods: Whole-body (13)C-leucine and (3)H-glucose kinetics were measured in the postabsorptive state and during an hyperinsulinemic, euglycemic, isoaminoacidemic clamp in 12 young men (age: 27 +/- 1 years; body mass index [BMI]: 23 +/- 1 kg/m(2)), 11 young women (age: 25 +/- 1 years; BMI: 21 +/- 1 kg/m(2)), 9 elderly men (age: 70 +/- 1 years; BMI: 26 +/- 1 kg/m(2)), and 10 elderly women (age: 69 +/- 2 years; BMI: 23 +/- 1 kg/m(2)).

The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism.

Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNG(PEP) (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2H nuclear magnetic resonance spectroscopy of plasma glucose.

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover.

Aims/hypothesis: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA.

The influence of sex on the protein anabolic response to insulin.

We hypothesize that sex influences whole-body protein anabolism in the postabsorptive state and in response to hyperinsulinemia. Kinetics of 3-(3)H-glucose and (13)C-leucine were studied in 16 men and 15 women after energy- and protein-controlled diets, before and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. In the postabsorptive state, women had 20% higher rates of leucine Ra (protein breakdown) and nonoxidative Rd (synthesis) adjusted for fat-free mass than men but net leucine balance was as negative.

Whole-body protein anabolic response is resistant to the action of insulin in obese women.

Background: Obesity is associated with insulin resistance of glucose and lipid metabolism.

Objective: We sought to determine the effects of obesity on the insulin sensitivity of protein metabolism.

Design: Whole-body [(13)C]leucine and [(3)H]glucose kinetics were measured in 9 lean and 10 obese women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp.

Increase in the thermic effect of food in women by adrenergic amines extracted from citrus aurantium.

Objective: To compare the thermic response to a meal between men and women of varied body composition and to determine whether adrenergic amines extracted from citrus aurantium (CA) induce an increase in metabolic rate and enhance the thermic response to the meal.

Research Methods And Procedures: In 30 healthy weight-stable subjects (17 women, 13 men; BMI: 20 to 42 kg/m2), body composition was determined by bioimpedance analysis followed by resting energy expenditure for 20 minutes, and the thermic effect of food (TEF) of a 1.7-MJ, 30-gram protein meal was determined intermittently for 300 minutes by indirect calorimetry.

The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in young subjects.

We propose that hyperinsulinemia stimulates protein synthesis when postabsorptive plasma amino acid (AA) concentrations are maintained. During a euglycemic hyperinsulinemic clamp, many AA, notably the branched-chain amino acids (BCAA), decline markedly. Therefore, we tested whether individual plasma AA could be maintained within the range of postabsorptive concentrations to assess the effects of insulin, infused at 40 mU/m(2) x min on whole-body protein and glucose metabolism, using [1-(13)C]-leucine and [3-(3)H]-glucose methodology.

Frailty amplifies the effects of aging on protein metabolism: role of protein intake.

Background: We previously showed that muscle contributes less to whole-body protein breakdown with healthy aging.

Objective: We hypothesized that frailty further compromises protein metabolism and that short-term protein supplementation improves protein status.

Design: Protein metabolism was studied with the oral, 60-h [(15)N]glycine and N(tau)-methylhistidine methods in 8 frail and 13 healthy elderly women during a 9-d isoenergetic, isonitrogenous formula diet and then after increased protein intakes in the frail women, to match the intakes of healthy subjects, for 12 d.

Combined infusion of epinephrine and norepinephrine during moderate exercise reproduces the glucoregulatory response of intense exercise.

Intense exercise (IE) (>80% O(2max)) causes a seven- to eightfold increase in glucose production (R(a)) and a fourfold increase in glucose uptake (R(d)), resulting in hyperglycemia, whereas moderate exercise (ME) causes both to double. If norepinephrine (NE) plus epinephrine (Epi) infusion during ME produces the plasma levels and R(a) of IE, this would prove them capable of mediating these responses. Male subjects underwent 40 min of 53% O(2max) exercise, eight each with saline (control [CON]), or with combined NE + Epi (combined catecholamine infusion [CCI]) infusion from min 26-40.

The prediction of resting energy expenditure in type 2 diabetes mellitus is improved by factoring for glycemia.

Background: Predictive equations have been reported to overestimate resting energy expenditure (REE) for obese persons. The presence of hyperglycemia results in elevated REE in obese persons with type 2 diabetes, and its effect on the validity of these equations is unknown.

Objective: We tested whether (1) indicators of diabetes control were independent associates of REE in type 2 diabetes and (2) their inclusion would improve predictive equations.

Prevention of type 2 diabetes.

The importance of type 2 diabetes is due to its high prevalence, the difficulties in achieving optimal glucose control (financial, time, quality of life) and the high frequency of chronic microvascular and macrovascular complications that add very significantly to the morbidity, mortality and overall cost of the disease. Numerous risk factors have been identified that predict the future onset of type 2 diabetes in individuals and an early stage of the disease (impaired glucose tolerance) can often be identified. Insulin resistance is central to the pathogenesis and is initially compensated by an increased insulin secretion.

Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes.

In intense exercise (>80% VO(2max)), unlike at lesser intensities, glucose is the exclusive muscle fuel. It must be mobilized from muscle and liver glycogen in both the fed and fasted states. Therefore, regulation of glucose production (GP) and glucose utilization (GU) have to be different from exercise at <60% VO(2max), in which it is established that the portal glucagon-to-insulin ratio causes the less than or equal to twofold increase in GP.