A major problem in replacing insulin in type I diabetes mellitus is that currently no depot preparation exists that is capable of mimicking the background insulin secretion of the healthy pancreas. Because all of the currently available intermediate- or long-acting insulin preparations have a peaked-action profile, excess insulin action at midnight and insulin waning at dawn occur whenever such an insulin preparation is given at supper time. If the target fasting plasma glucose is the ambitious near-normoglycemia of intensive insulin therapy, intermediate-acting insulin at suppertime easily results in hypoglycemia in the early evening hours and hyperglycemia in the fasting state. The problems of overnight glycemia in type I diabetes are further complicated by the dawn phenomenon and the Somogyi phenomenon. The dawn phenomenon is the combination of an initial decrease in insulin requirements between ∼2400 and ∼0300, followed by an increase in the insulin needs between ∼0500 and ∼0800. The dawn phenomenon is the result of changes in hepatic (and extrahepatic) insulin sensitivity, which are best attributed to nocturnal growth hormone secretion. The dawn phenomenon is a day-to-day reproducible event that occurs in nearly all diabetic patients. Its contribution to fasting hyperglycemia correlates with diabetes duration (inversely) and the HbAlc percentage (directly). Overall, it is estimated that the specific contribution of the dawn phenomenon to fasting hyperglycemia is ∼2 mM (∼35 mg/dl), but it may be much greater because of the waning of the depot-insulin preparation injected the previous evening. The Somogyi phenomenon, strictly speaking, refers to fasting hyperglycemia that occurs after inducement of nocturnal hypoglycemia by regular insulin. Because the present therapeutic regimens of NPH/Lente insulin given at suppertime cause overnight hyperinsulinemia, excessive fasting hyperglycemia rarely follows nocturnal hypoglycemia, except when excessive glucose is ingested to correct hypoglycemia. However, nocturnal hypoglycemia may easily deteriorate glycemic control later in the day, because it induces prolonged posthypoglycemic insulin resistance, which results in postbreakfast and late-morning hyperglycemia. With nocturnal insulin therapy, it is important to consider the problems of insulin pharmacokinetics, the dawn phenomenon, and the Somogyi phenomenon to prevent both nocturnal hypoglycemia and excessive fasting hyperglycemia. In programs of intensive insulin therapy aiming at a goal of near-normoglycemia in the fasting state, intermediate-acting insulin should be given at bedtime and should not be combined with regular insulin at suppertime. In programs of nonintensive insulin therapy, intermediateacting insulin can be injected with regular insulin at supper, but the fasting plasma glucose goal should be increased to 10–12 mM to prevent nocturnal hypoglycemia. In conclusion, insulin deficiency is the most important cause of fasting hyperglycemia in type I diabetes mellitus. However, insulin excess around midnight, which results from depot-insulin administration at suppertime, is the cause of frequent nocturnal hypoglycemia in type I diabetic patients. Correction of abnormal insulin pharmacokinetics by either splitting the evening insulin administration (intensive insulin therapy) or by increasing the targeted fasting plasma glucose (nonintensive insulin therapy) is the key to preventing nocturnal hypoglycemia and decreasing fasting hyperglycemia, thus improving overnight glycemic control in type I diabetes mellitus.
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December 01 1993
Nocturnal Blood Glucose Control in Type I Diabetes Mellitus
Geremia B Bolli, MD;
Geremia B Bolli, MD
Department of Internal Medicine and Endocrine and Metabolism and Sciences, University of Perugia
Perugia, Italy
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Gabriele Perriello, MD;
Gabriele Perriello, MD
Department of Internal Medicine and Endocrine and Metabolism and Sciences, University of Perugia
Perugia, Italy
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Carmine G Fanelli, MD;
Carmine G Fanelli, MD
Department of Internal Medicine and Endocrine and Metabolism and Sciences, University of Perugia
Perugia, Italy
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Pierpaolo De Feo, MD
Pierpaolo De Feo, MD
Department of Internal Medicine and Endocrine and Metabolism and Sciences, University of Perugia
Perugia, Italy
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Address correspondence and reprint requests to Geremia B. Bolli, MD, Dipartimento Medicina Interna e Scienze Endocrine e Metaboliche, Via E. Dal Pozzo, 06126 Perugia, Italy.
Citation
Geremia B Bolli, Gabriele Perriello, Carmine G Fanelli, Pierpaolo De Feo; Nocturnal Blood Glucose Control in Type I Diabetes Mellitus. Diabetes Care 1 December 1993; 16 (Supplement_3): 71–89. https://doi.org/10.2337/diacare.16.3.71
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