OBJECTIVE -To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA 1c .RESEARCH DESIGN AND METHODS -In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA 1c Ͼ7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) Յ100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA 1c , hypoglycemia, and percentage of patients reaching HbA 1c Յ7% without documented nocturnal hypoglycemia.RESULTS -Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA 1c (6.96 vs. 6.97%). A majority of patients (ϳ60%) attained HbA 1c Յ7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (Յ72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P Ͻ 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21-48% lower with glargine.CONCLUSIONS -Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA 1c in a majority of overweight patients with type 2 diabetes with HbA 1c between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.

A b b re v i a t i o n s : AUC, area under the curve; 1st PH, first-phase insulin release; Gluc, plasma glucose concentration during the OGTT; HOMA, homeostasis model assessment; IGT, impaired glucose tolerance; Ins, plasma insulin concentration during the OGTT; IR, insulin resistance index; ISI, insulin sensitivity index; ISI(comp), composite insulin sensitivity index; MCR, metabolic clearance rate; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; 2nd PH, second-phase insulin release; Secr, insulin release index; SI, sensitivity index; S y x , residual error of re g ression; WHR, waist-to-hip ratio.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Use of the Oral Glucose Tolerance Test to Assess Insulin Release and Insulin S e n s i t i v ity O R I G I N A L A R T I C L E O B J E C T I V E -The oral glucose tolerance test (OGTT) has often been used to evaluate a p p a rent insulin release and insulin resistance in various clinical settings. However, because insulin sensitivity and insulin release are interdependent, to what extent they can be pre d i c t e d f rom an OGTT is unclear.RESEARCH DESIGN AND METHODS -We studied insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 nondiabetic volunteers who had also undergone an OGTT. Demographic parameters (BMI, waist-to-hip ratio, age) and plasma glucose and insulin values from the OGTT were subjected to multiple linear re g ression to predict the metabolic clearance rate (MCR) of glucose, the insulin sensitivity index (ISI), and first-phase (1st PH) and second-phase (2nd PH) insulin release as measured with the respective clamps. R E S U LT S -The equations predicting MCR and ISI contained BMI, insulin (120 min), and glucose (90 min) and were highly correlated with the measured MCR (r = 0.80, P 0 . 0 0 0 0 5 ) and ISI (r = 0.79, P 0.00005). The equations predicting 1st PH and 2nd PH contained insulin (0 and 30 min) and glucose (30 min) and were also highly correlated with the measured 1st PH (r = 0.78, P 0.00005) and 2nd PH (r = 0.79, P 0.00005). The parameters predicted by our equations correlated better with the measured parameters than homeostasis model assessment for secretion and resistance, the 30-min insulin/ 30-min glucose ratio for secretion and insulin (120 min) for insulin resistance taken from the OGTT. C O N C L U S I O N S E p i d e m i o l o g y / H e a l t h S e r v i c e s / P s y c h o s o c i a l R e s e a r c h 296DIABETES CARE, VOLUME 23, NUMBER 3, MARCH 2000Insulin release and insulin sensitivity 0.5 kg/m 2 (19.7-45.8), and waist-to-hip ratio (WHR) 0.84 ± 0.10 (0.67-1.03); 65 had normal glucose tolerance (NGT), and the remainder had impaired glucose tolerance (IGT) according to the World Health O rganization criteria (1). Within 2 months, all subjects underwent a 75-g OGTT, a h y p e rglycemic clamp study in which the a rterialized venous plasma glucose concentration was increas...

Glargine provided less diurnal fluctuation in serum insulin levels than NPH and ultralente in healthy volunteers and patients with DMT1. This lower fluctuation of glargine over NPH or ultralente can help to reduce hyper- or hypoglycemia risks associated with insulin therapy and accordingly encourage achievement of better blood glucose control.

Sumatustatin inhibits buth insulin and glucagon secretion (Gerich, Lovinger and Grodsky (1975); its short-term infusion causes a transient decrease in plasma glucose followed by modest hyperglycemia in man (Lins and Efendic 1976; Sherwin. Hendler. DeFronzo. Wahren and Felig 1977), suggesting that insulin deficiency per se is sufficient to cause fasting hyperglycl'mia. If this is true, then prolonged inhibition of insulin secretion should result in persistent and more progressive hyperglycemia. On the other hand, if glucagon modifies the metabolic consequences of insulin defi· cieney, then prolonged inhibition of secretion of bolh insu· Iin and glucagun'might nut result in sustained hyperglycemia. To examine these alternatives, ehanges in plasma glucose, insulin, and glucagon, as weil as glucose turnover and glu· cose balance during prolonged infusions of somatostatin (for 12 hrs) were studied. Materials and MethodsInformed consent was ohtained from eight nonobese nor· mal subjects, six womcn, two men, aged 19·23 years. Four overnight-fasted subjects were studied on two occasions se· para ted by one week, once during 12 hr infusion of soma· tostatin (25 /lg/hr, courtesy 01' Doctors Jean Rivier and Roger Guillemin, Salk Institute, San Diego. California) and onee during a 12 hr infusion of 0.9 percent NaCI (0.5 mll minI. Another four subjects were studied once during 12 hr somatostatin infusions (\ 00 /lg/h). Blood was obtained at 30 min intervals throughout for plasma glucose (glucose oxidase, Yellow Springs Instrument A-23), glucose specific activity (Rizza and Gerich (\ 9791, insulin (Herbert. Lau, Gottlieb and Bleicher 1965) and glucagon (Faloona and Unger 19741. Glucose appearance (Ra) and disappearenee (Rdl were determined using primed-continuous infusions of [3H3] glucose (Rizza and Gerich 1979). Results and DiscussionInfusion of somatostatin at rates of 25 /lg/h (Fig. I) and IOD /lg/h (Table I) resulted in respective maximal increases in plasma glucose levels of 12 and 32 mg/d!. 80th plasma insulin and glucagon were suppressed approximately 25 percent during the 25 /lg/h somatostatin infusion; during the 100 /lg/h somatostatin infusion, plasma insulin was suppressed 50 percent while plasma glucagon was still suppressed 25 percent. The greater suppression of plasma insulin compared to that of glucagon I:ould account for the greater increment in plasma glucose observed with thc 100 /lg/h somatostatin infusion. Despite initial increases in plasma glucose, with continued infusion of somatostatin at both rates (and continued suppression of plasma insulin and glucagon), plasma glucose decreased to levels either not significantiy different from those in the same subjects infused with saline or to levels which wen: not significantly different from preinfusion levels. The transient hyperglycemia ohserved during infusion of somatostatin occurred as a result of a temporary im balance between rates of glucose production and utilization: thus, initiaily the rate, of both glucose production and glucose utilization decr...

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