John T. Hayford

A Survey of Cognitive Functioning at Different Glucose Levels in Diabetic Persons

Cognitive functioning was assessed in diabetic patients during hypoglycemia (60 mg/dl), euglycemia/ control (110 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels were set and maintained to within 4% of targeted levels by an artificial insulin/glucose infusion system (Biostator). Attention and fine motor skills, assessedby visual reaction time, was slowed at altered glucose levels. Performance was less impaired during hyperglycemia than hypoglycemia when a longer interstimulus interval was used,although it was still slower than normal. The time required to solve simple addition problems was increased during hypoglycemia, although reading comprehension was not affected. The possibility that some automatic brain skills are disrupted at altered glucose concentrations is discussed, while associative or inferential skills may be less affected.

Integrated Concentration of Growth Hormone in Juvenile-onset Diabetes

Twenty-four-hour patterns of plasma growth hormone concentrations were evaluated during 50 studies of 42 subjects with juvenile-onset diabetes mellitus. Blood was sampled continuously over 24 h using a portable peristaltic pump under conditions in which subjects remained ambulatory and maintained their daily dietary and insulin regimens. All diabetics showed diurnal patterns characterized by frequent episodes of secretion of growth hormone. The mean 24-h concentration of growth hormone, designated the integrated concentration, was significantly higher among juvenile-onset diabetics (P < 0.001) than it was in ageand sex-matched nondiabetic populations. Juvenileonset diabetics younger than 20 yr had significantly higher (P < 0.005) growth hormone integrated concentrations than did older juvenile-onset diabetics. There was no statistically significant correlation between the integrated concentrations of glucose and growth hormone; thus, the study failed to provide us with support for the hypothesis that elevated growth hormone concentrations in diabetics are a consequence of hyperglycemia. Variability of diurnal glucose concentrations was positively correlated (P < 0.015) with the growth hormone integrated concentration among juvenile-onset diabetics. Our observations indicate that rapid declines in plasma glucose concentration or episodes of absolute hypoglycemia were significant factors, contributing to both the elevated integrated concentration and the secretory spiking of growth hormone observed in the diabetic population,

Validity of urine glucose measurements for estimating plasma glucose concentration.

Both physicians and diabetic patients have traditionally relied on measurement of glycosuria as an indirect method of estimating plasma glucose concentration to guide adjustment of insulin and diet therapy. Our observations on the correlation between mean plasma glucose concentration with simultaneous urine glucose concentration or excretion rate re-emphasize the limitations of this approach. Although our observations show a significant correlation (P < 0.0001) between plasma glucose concentration and urine glucose concentration or urine glucose excretion rate, the wide confidence limits [95% confidence limits (minimum) ± 150 mg/dl] on plasma glucose concentration estimated from urine glucose measurements limit the clinical applicability of such estimates. Differences among subjects in the renal resorption of glucose contribute to the wide variance of estimates. However, significant variability in renal glucose resorption within individuals is documented, further reinforcing the limitations of urine glucose determinations for reliable estimates of plasma glucose concentrations. Diabetologists need to reconsider the applicability of urine glucose measurements in evaluation of adequacy of therapy and in adjustment of insulin dosage.

Free and total insulin integrated concentrations in insulin dependent diabetes.

Studies of the 24 hr insulin concentration profiles in diabetic subjects on chronic exogenous insulin have been hampered by the presence of endogenous anti-insulin antibody, which gives spurious estimates of radioimmunoassayable insulin concentrations. The introduction of polyethylene glycol precipitation of endogenous antibody has allowed development of reliable assays for determination of free and total insulin concentration in subjects on insulin therapy. This article reports our observations of plasma free and total insulin concentration in 50 Type I and Type II ambulatory insulin dependent diabetics, utilizing a continuous 24 hr blood withdrawal technique. In response to exogenous insulin, study subjects had marked elevations in insulin concentrations compared to controls. Mean free insulin integrated concentration was 3.5-fold higher in diabetics than nondiabetics. Mean total insulin integrated concentration was 868 microunits/ml, more than 20 times in excess of total insulin concentration in nondiabetics. There was a wide range among diabetics in the percentage of total insulin in the free insulin fraction. Neither free nor total insulin integrated concentration correlated with dose of exogenous insulin. Free and total insulin concentration profiles showed a limited range of variation in insulin concentration during the 24 hr of study, no subject having a profile that mimicked that observed in nondiabetic subjects. Glucose integrated concentration showed no correlation with free insulin integrated concentration, however, it did correlate inversely with the percentage of total insulin in the free insulin fraction. These data emphasize the difficulty in establishing normal patterns of insulin among diabetic subjects on conventional subcutaneous insulin therapy.

Glucose and Insulin Responses to Diet: Effect of Variations in Source and Amount of Carbohydrate

The influence of variations in amount of carbohydrate in the diet (45 per cent or 65 per cent of total calories) and source (sucrose or corn syrup) on plasma insulin and glucose concentrations was evaluated in eight normal men. Four diets, which were alternated in a Latin square design, were consumed for 10 days. Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test and over a 24-hour period while the test diets were consumed. The 24-hour study was completed with a portable, constant withdrawal pump, which allowed samples to be collected as a series of 48 consecutive, integrated, 30-minute samples. Thus, the 24-hour mean, or integrated, concentration as well as fluctuations during the day could be determined. The 24-hour integrated concentration of glucose did not vary significantly with the dietary changes tested. In contrast, two of the three methods used, to evaluate the glucose tolerance test results indicated that high carbohydrate diets improve glucose tolerance. Glucose fluctuations were significantly greater during ingestion of diets containing corn syrup than during those containing sucrose. The percentage of dietary energy supplied as carbohydrate did not influence glucose fluctuations significantly. Diets containing corn syrup were associated with significantly higher integrated concentrations of insulin than the sucrose diets. Insulin-integrated concentrations did not vary significantly with changes in the percentage of dietary carbohydrate. The insulin response to the glucose tolerance test did not vary with the source of carbohydrate and did not accurately reflect the 24-hour mean insulin concentrations. We concluded that (1) a change in the percentage of energy supplied as carbohydrate does not significantly influence the concentration of either glucose or insulin in normal subjects; (2) concentrations of glucose throughout the day are more stable when the dietary carbohydrate is sucrose than when it is corn syrup; (3) sucrose-containing diets require significantly lower insulin concentrations to maintain euglycemia than do corn syrup–containing diets; (4) glucose and insulin responses to an oral glucose tolerance test do not accurately reflect the 24-hour glucose and insulin concentrations obtained during ingestion of the test diets.

Triglyceride-integrated concentration: Relationship to insulin-integrated concentration☆☆☆

The relationship between plasma insulin and plasma triglyceride concentrations in response to diet alterations was studied in eight healthy adult male subjects. Four isocaloric formula diets, providing either 45% or 65% of total energy from carbohydrate and, using either sucrose or corn syrup as the carbohydrate source, were ingested for 10 days in a Latin Square sequence. Plasma triglyceride and insulin responses to diet alterations were assessed in blood samples after overnight fast and in samples obtained by a 24-hr continuous withdrawal technique, the mean concentrations of plasma insulin and plasma triglyceride during the 24-hr period of study were designated as the insulin-integrated concentration and triglyceride-integrated concentration respectively. Mean insulin integrated concentrations were 45% to 57% higher and mean triglyceride integrated concentrations 19% to 27% lower during ingestion of analogous diets containing sucrose. Increases in the percentage of total energy supplied as carbohydrate did not significantly change the insulin integrated concentration. Seven of the eight subjects had higher insulin-integrated concentrations associated with lower triglyceride-integrated concentrations during the four diet periods (r ranged from −.536 to −.777), while one subject had a positive correlation (+.324). There was a statistically significant (p < .01) inverse relationship between the mean insulin- and triglyceride-integrated concentrations during the four diet periods.

EFFECT OF VARIOUS CARBOHYDRATE |[lpar]|CHO|[rpar]| DIETS ON FASTING TRIGLYCERIDE |[lpar]|F TRIG|[rpar]| AND 24 HOUR TRIGLYCERIDE CONCENTRATIONS |[lpar]|TRIG IC|[rpar]|

The conclusion that a high CHO diet results in hypertrigly-ceridemia has been based entirely on F Trig values. This study was designed to evaluate the effects of variations in CHO intake on Trig IC as well as F Trig. Four diets were studied: 45% sucrose (A), 65% sucrose (B). 45% corn syrup (C), and 65% corn syrup (D). All diets included 15% protein and 300 mg. of cholesterol. The eight subjects consumed the constant liquid diets in random order (Latin square design) for 10 days prior to the 24 hour constant blood withdrawal study which provided the mean 24 hour triglyceride concentration or Trig 1C.Conclusions: 1. The F Trig does not accurately reflect the Trig 1C. 2. F Trig levels correlate with amount of carbohydrate. 3. Trig IC levels correlate with type of carbohydrate with higher Trig IC occurring during sucrose ingestion. 4. A high carbohydrate diet per se does not result in hypertriglyceridemia.