Pentti Seppälä

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.

C-peptide determination in the choice of treatment in diabetes mellitus

The predictive value of the intravenous glucagon test in assessing the requirement of insulin therapy in diabetes mellitus was evaluated in 105 adult diabetics. Basal and stimulated C-peptide concentrations and increments of C-peptide concentration were examined separately among newly and previously diagnosed diabetics. The poststimulatory C-peptide concentration of 0.6 nmol/l (Novo, antibody M 1230) proved to be the most reliable basis for the choice of therapy. Adequate therapy could have been assessed in 70 cases (67%) without glucagon stimulation. To derive maximal information of plasma C-peptide concentrations, a biphasic scheme of the use for C-peptide determinations and glucagon stimulation is presented. Basal and stimulated C-peptide levels of insulin-requiring diabetics correlated negatively with the duration of diabetes but they did not correlate with the relative body weights. Basal and stimulated C-peptide levels of non-insulin-requiring diabetics did not correlate with the duration of diabetes, but they correlated positively with the relative body weights.

Plasma and urinary C-peptide in the classification of adult diabetics

Plasma and urinary C-peptide determinations in the discrimination between insulin-requiring and non-insulin-requiring diabetes were elevated in 61 adult diabetics. Specimens for C-peptide determinations were taken on two consecutive days: on the first day plasma C-peptide concentrations were determined before and 6 min after intravenous glucagon administration. On the second day 2- and 4-h urinary C-peptide excretion was measured after an individual breakfast. Results of urinary C-peptide analyses were expressed as molar concentration and also as molar quantity excreted (without any corrections and related to creatinine excretion). Glucagon-stimulated plasma C-peptide turned out to be a reliable criterion for the detection of insulin requirement. Sixty-nine per cent of diabetics included in this study were classifiable by basal plasma C-peptide concentrations. Two-hour postprandial urinary C-peptide/creatinine quotient turned out to be slightly less sensitive (89%) than the glucagon test (94%) and of equal specificity (96%). Glucagon-stimulated plasma C-peptide and postprandial urinary C-peptide excretion correlated significantly among insulin-requiring diabetics (r = 0.73), but not among non-insulin-requiring diabetics (r = 0.23). We regard determination of stimulated plasma C-peptide as a primary investigation for the direct assessment of endogenous insulin secretory reserves for clinical management decisions. Determination of postprandial urinary C-peptide is applicable in selected situations for non-invasive assessment of insulin secretion.

Redundant colon as a cause of constipation

The authors present evidence to show that a long colon is associated with constipation. In certain cases of intractable constipation associated with a long colon they recommend surgical treatment.

Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes

Abstract. In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non‐insulin‐dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L‐1, range 15–1550 mg L‐1 vs. 157 mg L‐1, range 15–919 mg L‐1, NS and 92, range 15–1190 mg L‐1 vs. 103 mg L‐1, range 15–842 mg L‐1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg ‐1L, but this effect was not related to the concomitant improvement in metabolic control (mean change (±SEM) of HbA1c from 9.80±0.15 to 8.00±0.12; P < 0.001). In subjects with elevated Lp(a) concentrations (>300 mg L‐1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may modulate the concentration of Lp(a).

Effect of acidification on the electrophoretic pattern of anacid gastric juice.

SummaryThe electrophoretic pattern of the gastric juice of persons with achlorhydria and with pernicious anemia undergoes marked changes after acidification of the sample for 15 min. (to pH 1–2). Band M4 especially becomes weaker or disappears completely. Bands M2 and M3 frequently are weaker, and the albumin content is reduced in many cases. At the same time there often appears a cathodic band X+Y+Z. The changes are probably a result of the rapid degradation of gastric albumin and mucous substances in the acid medium, with consequent release of polypeptides.

Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism

This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.