Citations

Two interpretations of the Boston Naming Test (BNT) discontinuation rule of "six consecutive failures" were uncovered in an informal survey. The rigorous interpretation includes correct responses to phonemic cues in the count of failures, whereas the lenient interpretation does not. Using both methods to score the same protocols, BNT final scores were changed in 3% of 655 normal elderly persons and in 31% of 140 patients with Alzheimer's Disease (AD). Among normals, discrepant scores were most often found in persons age 80 years and older, and scores differed by up to 16 points. Among AD patients, discrepant scores did not preferentially occur in any age group, but scores differed by up to 10 points. The clinical impact of BNT scoring differences occasionally can be substantial and warrants attention.

Lipolysis of adipose tissue triglycerides releases glycerol. Twenty-four volunteers, of whom 6 were obese and 13 were women, received a primed-constant infusion of 2H5-glycerol for 120 min during postabsorptive steady-state conditions. Arterial, abdominal venous, and interstitial (microdialysis) samples were taken, and a four-compartment model was applied to assess subcutaneous abdominal adipose tissue glycerol kinetics. Adipose tissue blood flow was measured using 133Xe washout. Venous glycerol concentrations (median 230 μmol/l [interquartile range 210–268]) were consistently greater than those of arterial blood (69.1 μmol/l [56.5–85.5]), while glycerol isotopic enrichments (tracer-to-tracee ratio) were greater in arterial blood (8.34% [7.44–10.1]) than venous blood (2.34% [1.71–2.69], P < 0.01). Microdialysate glycerol enrichment was 1.44% (1.11–1.79), indicating incomplete permeability of glycerol between capillary blood and interstitium. Calculated interstitial glycerol concentrations were between 270 μmol/l (256–350) and 332 μmol/l (281–371) (examining different boundary conditions). The calculated capillary diffusion capacity (ps) was between 2.21 ml · 100 g tissue−1 · min−1 (1.31–3.13) and 3.09 ml · 100 g tissue−1 · min−1 (1.52–4.90) and correlated inversely with adiposity (Rs ≤ −0.45, P < 0.05). Our results support previous estimates of interstitial glycerol concentration within adipose tissue and reveal capillary diffusion capacity is reduced in obesity.

Little is known about the fate of the lipolytic products produced by the action of lipoprotein lipase (LPL) on circulating triglyceride-rich lipoproteins in humans. We studied eight lean, healthy male subjects after an overnight fast. Subjects received infusions of lipid emulsions containing triolein labeled with 3H on both the glycerol backbone and the fatty acid portion of the molecule; 14C glycerol and 14C oleate were coinfused to quantify the systemic and forearm release of 3H glycerol and 3H oleate resulting from LPL action. There was significant forearm uptake of both whole plasma triglyceride (presumed to represent primarily VLDL; extraction fraction 2.6 ± 0.6%, P < 0.005 vs. zero) and radiolabeled triglyceride derived from the lipid emulsion (a surrogate for chylomicrons; extraction fraction 31 ± 4%, P < 0.005 vs zero). Systemic clearance and forearm fractional extraction of glycerol was greater than that of oleate (P < 0.001 and P < 0.02, respectively). The systemic and forearm fractional release of LPL-generated glycerol were similar at 51 ± 4 and 59 ± 1%, respectively (NS). In contrast, the forearm fractional release of LPL-generated oleate was less than systemic fractional release (14 ± 2 vs. 36 ± 4%, P < 0.0001). These results indicate that there is escape, or spillover, of the lipolytic products of LPL action on triglyceride-rich lipoproteins in humans. They further suggest that LPL-mediated fatty acid uptake is an inefficient process, but may be more efficient in muscle than in adipose tissue.

Both basal and postprandial pancreatic polypeptide (PP) concentrations were exaggerated twofold in lean NIDDM patients, whereas they were normal in lean IDDM and obese NIDDM patients who were hyperglycemic as a result of partial insulin withdrawal. Insulin infusion from an artificial endocrine pancreas, which resulted in fasting euglycemia and near-normoglycemia postprandially, had no effect on PP responses in any of the diabetic patients. No postprandial PP responses were observed in totally pancreatectomized (TPX) patients. Excessive basal and postprandial concentrations of PP in diabetes appear to be related to both leanness and residual beta cell function and, therefore, potential markers for lean NIDDM.

Since little is known regarding the appropriate time for preprandial insulin administration, we compared the effects of 30-min subcutaneous insulin infusions started 60 min, 30 min, and immediately before meal ingestion on postprandial plasma glucose and insulin profiles in eight subjects with insulin-dependent diabetes mellitus. Of these three regimens, administration of insulin 60 min before meal ingestion provided plasma glucose and insulin profiles closest to normal and permitted less insulin to be used. Our results suggest that adjustments in the timing as well as in the amount of insulin administered preprandially may be used in the management of diabetes and that prolonging the interval between administration of insulin and meal ingestion may reduce insulin requirements and thus decrease the hyperinsulinemia usually associated with insulin therapy.

Glucagon normally plays a primary role in promoting glucose recovery from insulin-induced hypoglycemia. Epinephrine compensates largely for deficient glucagon secretion. Glucose recovery from hypoglycemia fails to occur only in the absence of both glucagon and epinephrine. Perhaps as a relatively early feature of autonomic neuropathy, patients with insulin-dependent diabetes mellitus commonly have blunted or absent glucagon secretory responses to hypoglycemia. However, this deficient response is commonly compensated for by epinephrine and glucose recovery occurs. In some patients, progression of adrenergic neuropathy to the point of deficient epinephrine secretory responses to hypoglycemia, coupled with deficient glucagon responses, leads to frequent, severe, and prolonged hypoglycemia. Thus, these glucose counterregulatory systems are of critical importance to patients with insulindependent diabetes mellitus. The efficacy of glucose counterregulation in a given patient may determine the degree to which euglycemia can be achieved with aggressive insulin therapy in that patient.

Although initial laboratory studies using biosynthetic human insulin (BHI) indicate little difference in the intrinsic potency of biosynthetic human and purified pork insulin (PPI) in vitro, certain in vivo observations suggest that BHI may differ pharmacokinetically from pork insulin. If further studies support these suggestions, the use of BHI may be able to provide better glycemic control and more near normal plasma insulin profiles during treatment of insulin-dependent diabetes than can be achieved with presently available insulin preparations. However, BHI appears to offer no advantage over presently available PPI in terms of prevention and treatment of insulin lipodystrophy, insulin allergy, and immune insulin resistance.

To assess the feasibility of preprogramming an open-loop device with insulin flow rates generated by the Biostator Glucose Controller, comparisons were made in 10 juvenile-onset diabetic patients between meals of equal size and composition taken in the morning, at noon, and in the evening and a bedtime snack during a 24-h period of Biostator glucose control. Four additional diabetic patients had Biostator glucose control for 72 h. Similar amounts of insulin were infused for the meals taken at differing times of the day and, except for the morning meal, for the same meal on two successive days. The meal-related glycemic patterns expressed as mean indices of meal excursions (MIME) were similar for meals of identical size and composition during a single day and for the same meal taken on two consecutive days. Preliminary results using an open-loop device preprogrammed by the Biostator system, although encouraging, underscore the deficiency of the subcutaneous route viz. the delayed entry of insulin into the circulation in achieving normal glucose levels and patterns.

Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.