Our aims were (1) by computed tomography (CT) to establish a population database for pancreas volume (parenchyma and fat) from birth to age 100 years, (2) in adults, to establish the impact of gender, obesity, and the presence or absence of type-2 diabetes on pancreatic volume (parenchyma and fat), and (3) to confirm the latter histologically from pancreatic tissue obtained at autopsy with a particular emphasis on whether pancreatic fat is increased in type-2 diabetes. We measured pancreas volume in 135 children and 1,886 adults (1,721 nondiabetic and 165 with type-2 diabetes) with no history of pancreas disease who had undergone abdominal CT scan between 2003 and 2006. Pancreas volume was computed from the contour of the pancreas on each CT image. In addition to total pancreas volume, parenchymal volume, fat volume, and fat/parenchyma ratio (F/P ratio) were determined by CT density. We also quantified pancreatic fat in autopsy tissue of 47 adults (24 nondiabetic and 23 with type-2 diabetes). During childhood and adolescence, the volumes of total pancreas, pancreatic parenchyma, and fat increase linearly with age. From age 20-60 years, pancreas volume reaches a plateau (72.4 +/- 25.8 cm(3) total; 44.5 +/- 16.5 cm(3) parenchyma) and then declines thereafter. In adults, total ( approximately 32%), parenchymal ( approximately 13%), and fat ( approximately 68%) volumes increase with obesity. Pancreatic fat content also increases with aging but is not further increased in type-2 diabetes. We provide lifelong population data for total pancreatic, parenchymal, and fat volumes in humans. Although pancreatic fat increases with aging and obesity, it is not increased in type-2 diabetes.
Introduction According to the ‘vicious cycle’ hypothesis proposed by Dr Stokes, sensitivity to load has been implicated in the progression of spinal deformity during growth due to the reaction of vertebrae to mechanical loads on their growth plate. Mechanical loads on the vertebrae are altered by the mechanical stiffness of the spinal implant. Unfortunately , the relationship between the implant stiffness and the modulation of spinal growth is not quantified. This review aims to analy se the study investigating the effect of implant stiffness on this growth using experimental and finite element techniques. Materials and methods In vitro and finite element studies involving multiple pig spines and segments (T1–T4, T5–T8, and T9–T12) were used. Springs of varying length (320 N/m stiffness) and a metal link (64.5 × 10 6 N/m stiffness) were attached to adjacent vertebrae and the spines distracted to model growth. Discussion It is shown that the addition of an implant to the spinal column will increase the stiffness of the spine. Furthermore, as the stiffness increases, the distraction of the spine decreases. In addition, asymmetric placement of the implant leads to r otation of the spine segment during distraction. Conclusion Spinal devices with different mechanical properties yield variable stiffness of the spine segments, as well as displacement and rotations, which will further affect the longitudinal growth of the spine.
The estimation of the time course of hepatic glucose production in non-steady state is of great physiopathological interest. The approach which is most widely used to estimate hepatic glucose production is based on the use of simple approximate models whose domain of validity is limited. In this paper we propose a novel, general approach to study the transition from the basal to an euglycemic. hyperinsulinemic state during a dual tracer experiment performed in humans. The approach is based on a physiological model of the glucoseinsulin system and deconvolution. The use in the deconvolution algorithm of the calculated endogenous glucose concentration, instead of the measured total glucose concentration, is
To determine whether glucose-mediated as well as insulin-mediated regulation of glucose utilization and glucose production is impaired in patients with insulindependent diabetes mellitus (IDDM), six nonobese, diabetic patients and seven age-, sex-, and weightmatched nondiabetic subjects were studied. Despite slightly higher free insulin concentrations in the diabetic patients than in the nondiabetic subjects during 0.2 mU/kg · min (22 ± 3 versus 15 ± 2 μU'ml) and 1.0 mU'kg · min (98 ± 10 versus 75 μU/ml) insulin infusions, glucose utilization at plasma glucose concentrations of 95, 135, and 175 mg/dl was lower in the diabetic patients than in the nondiabetic subjects. The increment in glucose utilization per increment in plasma glucose (i.e., slope) in the diabetic and nondiabetic subjects, respectively, did not differ significantly during either the 0.2 (1.7 ±1.3 versus 1.4 ± 0.5 dl/kg · min) or 1.0 (4.4 ±1.1 versus 6.2 ±1.0 dl/kg · min) mU/kg · min insulin infusions, although they tended to be higher in the nondiabetic subjects during the latter infusion. Thus, although stimulation of glucose utilization by insulin is impaired in patients with IDDM, the ability of an increase in glucose concentration to increase glucose utilization does not appear to differ from that present in nondiabetic subjects, at insulin concentrations in the low physiologic range. Whether differences exist in the high physiologic range remains to be determined.
The present studies were undertaken to determine whether people with type 2 diabetes are resistant to the effects of glucose as well as insulin. Diabetic and nondiabetic subjects were studied on three occasions. Hormone secretion was inhibited with somatostatin. Insulin concentrations were kept at "basal" levels (referred to as low insulin infusion) from 0 to 180 min then increased to approximately 200 pmol/l from 181 to 360 min (referred to as high insulin infusion). Glucose concentrations were clamped at either approximately 95, approximately 130, or approximately 165 mg/dl on each occasion. In the presence of basal insulin concentrations, a progressive increase in glucose from 95 to 130 to 165 mg/dl was accompanied by a comparable and progressive decrease (P = 0.001 to 0.003 by analysis of variance [ANOVA]) in endogenous glucose production (measured with [6-(3)H]glucose) and total glucose output (measured with [2-(3)H]glucose) and incorporation of 14CO2 into glucose (an index of gluconeogenesis) in both diabetic and nondiabetic subjects, indicating normal hepatic (and perhaps renal) response to glucose. In the nondiabetic subjects, an increase in glucose concentration from 95 to 130 to 165 mg/dl resulted in a progressive increase in glucose disappearance during both the low (19.9 +/- 1.8 to 23.6 +/- 1.8 to 25.4 +/- 1.6 micromol x kg(-1) x min(-1); P = 0.003 by ANOVA) and high (36.4 +/- 3.1 to 47.6 +/- 4.5 to 61.1 +/- 7.0 micromol x kg(-1) x min(-1); P = 0.001 by ANOVA) insulin infusions. In contrast, in the diabetic subjects, whereas an increase in glucose from 95 to 130 mg/dl resulted in an increase in glucose disappearance during both the low (P = 0.001) and high (P = 0.01) dose insulin infusions, a further increase in glucose concentration to 165 mg/dl had no further effect (P = 0.41 and 0.38) on disappearance at either insulin dose (low: 14.2 +/- 0.8 to 18.2 +/- 1.1 to 18.7 +/- 2.4 micromol x kg(-1) x min(-1); high: 21.0 +/- 3.2 to 33.9 +/- 6.4 to 32.5 +/- 8.0 micromol x kg(-1) x min(-1) for 95, 130, and 165 mg/dl, respectively). We conclude that whereas glucose-induced stimulation of its own uptake is abnormal in type 2 diabetes, glucose-induced suppression of endogenous glucose production and output is not. The abnormality in uptake occurs in the presence of both basal and high insulin concentrations and is evident at glucose concentrations above but not below 130 mg/dl, implying a defect in a glucose-responsive step.
Studies with tritiated isotopes of glucose have demonstrated that hyperglycemia per se stimulates glucos utilization and suppresses glucose production in humans. These conclusions rely on the assumption that tritiated glucose provides an accurate measure of glucose turnover. However, if in the presence of hyperglycemia the isotope either loses its label during “futile” cycling or retains its label during cycling through glycogen, then this assumption is not valid. To examine this question, glucose utilization and glucose production rates were measuredin nine normal subjects with a simultaneous infusion of [23H]glucose, an isotope that may undergo futile cycling but does not cycle through glycogen; [614C]glucose, an isotope that may cycle through glycogen but does not futile cycle; and [33H]glucose, an isotope that can both undergo futile cycling and cycle through glycogen. In the postabsorptive state at plasma glucose concentration of 95 mg dl−1, glucose turnover determined with [614C]glucose (2.3 ±0.1 mg kg−1 min−1) was greater than that determined with [33H]glucose (2.1 ± 0.1 mg kg−1 min−1 P = 0.002) and slightly less than that determined with [23H]glucose (2.7 ± 0.2 mg kg−1 min−1 P = 0.08). Plasma glucose was then raised from 95 to 135 to 175 mg dl−1 while insulin secretion was inhibited, and circulating insulin, glucagon, and growth hormone concentrations were maintained constant by infusion of these hormones and somatostatin. Glucose production and utilization rates determined with [614C]-glucose continued to be less than those determined with [23H]glucose and greater than those seen with [33H]glucose. However, the decrements in glucose production and increments in glucose utilization were identical with all isotopes. Glucagon was then infused at a high rate to stimulate endogenous glucose release. This resulted in a significant (P < 0.05) increase in both [614C]- and [33H]- but not [23H]giucose, indicating release of the former two isotopes from glycogen. This resulted in a significantly lower (P < 0.04) estimate of glucose production and utilization during the glucagon infusion determined with [614C]- and [33H]glucose compared with that determined with [23H]glucose. Thus, whereas neither [23H]- nor [33H]glucose precisely reflect glucose turnover measured by [614C]glucose, all three isotopes provide an equivalent assessment of the effects of hyperglycemia on glucose production and utilization in humans. However, release of either [614C]- or [33H]glucose from glycogen may result in an underestimate Of glucose turnover.
