Effect of glycemic control on growth velocity in children with IDDM.

OBJECTIVE: To determine the effect of glycemic control on growth velocity in children with insulin-dependent diabetes mellitus. RESEARCH DESIGN AND METHODS: One hundred twenty-two children with insulin-dependent diabetes mellitus were studied over a 5-yr period. Every 4 mo, glycemic control was assessed by measuring total glycosylated hemoglobin (GHb), pubertal status was determined by physical examination, and height was measured with a stadiometer. Height measurements were normalized for age and sex by converting them to tau scores (the number of SD above or below the mean for age and sex). Alterations in growth velocity were determined by the change in tau scores (delta tau) between visits (i.e., no change in tau score = normal growth velocity; decrease in tau score = growth deceleration; and increase in tau score = growth acceleration). RESULTS: A linear relationship was seen between GHb levels and the change in tau scores (r = -0.117, P = 0.001). GHb values less than 8% were associated with growth acceleration (delta tau = +0.10 +/- 0.03), and the greatest growth deceleration occurred when GHb was greater than 16% (delta tau = -0.07 +/- 0.03). The level of GHb at which growth suppression occurred (mean delta tau became negative) was dependent on pubertal status: Tanner stage 1 greater than or equal to 10%, Tanner stages 2 and 3 greater than or equal to 8%, Tanner stages 4 and 5 greater than or equal to 16%. CONCLUSIONS: Linear growth velocity in children with insulin-dependent diabetes mellitus is heavily related to metabolic control. Children who are prepubertal or in the early stages of puberty are the most vulnerable to growth suppression. Once puberty is well established, growth suppression does not occur until marked hyperglycemia (GHb greater than 16%) exists.

Effect of sucrose-containing snacks on blood glucose control.

To determine whether ingestion of sucrose-containing snacks would affect blood glucose (BG) control, 16 subjects with insulin-dependent diabetes mellitus participated in a 5-day double-blind study at a diabetes camp. Eight subjects in the sucrose group ate sucrose-sweetened snacks twice a day, and 8 subjects in the control group ingested snacks that were sweetened with aspartame. The percentage of total daily calories derived from added sucrose was 7% for the sucrose group and 1% for the control group. Metabolic control was assessed by daily capillary BG measurements obtained before meals and the bedtime snack and by determination of serum fructosamine (F) concentrations on arrival at camp (day 0) and after 5 days on the study protocol (day 5). No significant difference was seen between the groups on day 0 (sucrose group [mean +/- SD]: BG 9.9 +/- 3.6 mM, F 3.54 +/- 0.38 mM; control group: BG 9.1 +/- 2.8 mM, F 3.74 +/- 0.71 mM) or day 5 (sucrose group: BG 8.8 +/- 2.6 mM, F 2.94 +/- 0.32 mM; control group: BG 7.4 +/- 2.8 mM, F 2.92 +/- 0.59 mM). We conclude that ingestion of sucrose, added to snacks in an amount up to 7% of total energy intake, does not adversely affect short-term BG control.

Standard parameters of diabetic control: are they reliable?

To evaluate the reliability of the tradional methods to assess short-term control of diabetes, 25 children with insulin-dependent diabetes were studied with a 24-h glucose profile in addition to the traditional assessment techniques. Patient compliance was elminated as much as possible from the experimental design. The correlation of the routine methods with the 24-h glucose profile was excellent, and a scoring system for control was empirically derived. The single method of assessment that correlated best with the overall control score was the traditional daily urine test. In 6 of the 25 subjects studied, relative hypoglycemia was observed, occurring asymptomatically at night, and was followed by a hyperglycemic rebound. Traditional assessment techniques did not detect this event. Five additional patients had symptomatic daytime hypoglycemia. We conclude that the traditional daily urine tests are adquate indicators of day-to-day control in most diabetic patients, given adquate compliance. Our data also suggest that asymptomatic nocturnal hypoglycemia occurs frequently in children with diabetes, although clinical proof is difficult in the absence of a 24-h glucose profile.

The hepatic extraction of gastric inhibitory polypeptide and insulin.

The hepatic extractions of gastric inhibitory polypeptide (GIP) and insulin were determined using in vitro and in vivo methods to assess the role of the liver in GIP metabolism and the possible effect of GIP on the hepatic extraction of insulin. During in vitro studies using the isolated perfused rat liver, infusion of GIP (2000 pg/ml) alone and in combination with porcine insulin (200 microU/ml) resulted in negligible hepatic extraction of immunoreactive GIP (IR-GIP) in both fed and fasted animals during either physiologically euglycemic or hyperglycemic perfusions. Hepatic extraction of insulin, however, ranged from 26-36% in fasted animals and from 7-25% in fed animals. Hepatic extraction of insulin and net hepatic glucose appearance were minimally affected by GIP. In vivo studies in awake dogs were then performed, in which simultaneous portal and peripheral venous levels of IR-GIP, immunoreactive insulin (IRI), and glucose were assessed after intraduodenal glucose administration. The portal to peripheral (PORT/PERI) venous ratio of endogenous IRI and IR-GIP reflected the findings of the in vitro studies; the PORT/PERI ratio of IRI levels rose from a basal value of 1.9 +/- 0.3 to a peak of 3.7 +/- 0.9, while the PORT/PERI ratio of IR-GIP levels rose from a basal value of 1.0 +/- 0.1 to a peak of 1.4 +/- 0.2, then rapidly returned to 1.0. The in vivo data are consistent with a continuous hepatic extraction of 40-50% of the insulin entering the liver and a negligible hepatic extraction of IR-GIP. We conclude that hepatic extraction of GIP in vitro or in vivo is minimal. In addition, while the fed state of the animal before infusion can result in changes in the in vitro hepatic extraction of insulin, GIP does not mediate these changes.

Phenotypic features of patients with congenital adrenal hypoplasia and glycerol kinase deficiency.

Two unrelated boys with congenital adrenal hypoplasia and glycerol kinase deficiency were found to have similar features, including characteristic facies, testicular abnormalities, short stature, psychomotor retardation, and muscular dystrophy. The resemblance of these boys to other patients described in the literature suggests that a distinct phenotypic syndrome occurs in children with congenital adrenal hypoplasia and glycerol kinase deficiency.