Observations on Blood Lipid and Intermediary Metabolite Concentrations During Conventional Insulin Treatment or CSII

Abstract

An objective of The Kroc Collaborative Study Group trial of the feasibility of maintaining improved control of plasma glucose concentrations with continuous subcutaneous insulin infusion (CSII) was to test the non-glycemic aspects of metabolic control in relation to microvascular disease. Serum lipid levels were assessed in the 68 patients completing the 8-mo trial, before and after randomization to conventional insulin treatment (CIT) or CSII. During CSII, fasting serum cholesterol concentrations, normal at baseline (186 +/- 7 mg/dl), were unchanged at 4 and 8 mo (183 +/- 8 and 186 +/- 10 mg/dl). Fasting serum triglyceride concentrations fell on treatment with CSII (baseline 90 +/- 12 mg/dl, 8 mo 60 +/- 7 mg/dl, P less than 0.01), but were unchanged during CIT (baseline 88 +/- 8 mg/dl, 8 mo 83 +/- 10 mg/dl). Thirty-two patients in three centers had 24-h profiles of intermediary metabolites measured at baseline (0), 4, and 8 mo. Mean 24-h venous blood lactate levels fell during CSII (baseline 1.28 +/- 0.12 mmol/L, 4 mo 0.99 +/- 0.4 mmol/L, P less than 0.05; 8 mo 1.05 +/- 0.11 mmol/L), but blood alanine levels were unchanged. Venous blood 3-hydroxybutyrate fell from 0.12 X /divided by 1.18 mmol/L at baseline to 0.06 X /divided by 1.22 mmol/L at 8 mo during CSII (P less than 0.01), mainly due to decreases at 0400 and 0600 h. Decreases in fasting serum triglyceride levels confirm previous investigations of insulin-dependent diabetic subjects treated with CSII; decreases of venous blood lactate and 3-hydroxybutyrate levels toward normal indicate that these metabolic effects of CSII recognized in short-term studies are sustained over an 8-mo period.

Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion

“…Six months of CSII treatment, however, suppressed the mean diurnal concentration to normal levels (Fig. IB) corro¬ borating previous results (Beck-Nielsen et al 1985;Lawson et al 1985;Pickup et al 1979). In contrast, the lactate levels remained unchanged in the UCT group after 6 months of observation.…”

“…Since 1978, when the first studies with continuous subcutaneous insulin-infusion (CSII) pumps were reported (Pickup et al 1978), evidence has ac¬ cumulated that CSII provides improved glycae¬ mic control (Beck-Nielsen et al 1985;Buysschaert et al 1983;Chiasson et al 1984;Gooch et al 1984;Lawson et al 1985;Pickup et al 1978Pickup et al , 1979Rizza et al 1980;Steno Study Group 1982;Tamborlane et al 1979aTamborlane et al , 1985. Although em¬ phasis in the assessment of diabetic control has usually been on glucose metabolism, insulin-de¬ pendent diabetes affects a variety of metabolites and hormones, some of which may play a patho¬ genic role in diabetic complications.…”

“…Although em¬ phasis in the assessment of diabetic control has usually been on glucose metabolism, insulin-de¬ pendent diabetes affects a variety of metabolites and hormones, some of which may play a patho¬ genic role in diabetic complications. Relatively few reports have inquired whether other metabolites or hormones known to be deranged in unchanged conventional insulin therapy (UCT) are improved during CSII treatment in insulin-deficient dia¬ betes mellitus (Beck-Nielsen et al 1985;Chiasson 1984;Gooch et al 1984;Lawson et al 1985;Pickup et al 1979;Tamborlane et al 1979a). …”

Glycemic Control and Diabetic Complications

“…Maintenance of near normoglycemia for 4 -5 wk with use of a portable insulin infusion pump resulted in a significant reduction of glucagon levels to within the normal range (54). Similarly, normalization of blood glucose with insulin pump therapy resulted in the reduction of intermediate metabolites including lactate, 3-hydroxybutyrate, and alanine (55,56). Growth hormone and catecholamine responses to exercise normalized after 7-14 days of pump therapy (57).…”

“…Several investigators demonstrated that near-normalization of blood glucose resulted in significant reductions in levels of plasma cholesterol, triglycerides, free fatty acids, and plasma apoprotein B (56,64,65). Raskin observed that as little as 3 wk of euglycemia resulted in significant decreases in plasma cholesterol, VLDL and LDL cholesterol, plasma triglycerides, and VLDL triglyceride levels (66,67).…”