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PubMed1976

Studies on a protamine (galline) from fowl sperm. 3. The total amino acid sequence of intact galline molecule.

Of the eight fractions (G-I-G-VIII) obtained from galline, a protamine from rooster sperm nuclei, the complete amino acid sequences of two fractions G-I and G-V have already been reported. Other fractions of galline purified repeatedly on the column of Bio-Gel CM-30 were submitted to structural analyses. The complete amino acid sequences of three (G-II, G-III and G-VII) of the fractions and the partial chemical structures of two (G-VI and G-VIII) of the fractions were established from the results of analyses of the tryptic and chymotryptic peptides together with those of end groups and terminal sequences. Remarkable similarities have so far been found in the sequences of these fractions. Combining these results with those complementarily explained in the following paper, it was finally confirmed that the intact galline molecule is composed of only one molecular species (G-VIII) and that fractions (G-I-G-VII) were derived from G-VIII by the action of an inherent protease in the preparation process. Consequently, the total amino acid sequence of the intact galline is concluded to be as follows: H-Ala-Arg-Tyr-Arg-Ser-Arg-Gly-Arg-Ser-Arg-Ser-Arg-Arg-Thr-Arg-Arg-Arg-Arg-Ser-Pro-Arg-Ser-Gly-Arg-Arg-Arg-Ser-Pro-Arg-Arg-Arg-Arg-Ser-Arg-Arg-Arg-Arg-Arg-Tyr-Gly-Ser-Ala-Arg-Arg-Ser-Arg-Arg-Ser-Gly-Gly-Val-Arg-Arg-Arg-Arg-Tyr-Gly-Ser-Arg-Arg-Arg-Arg-Arg-Arg-Tyr-OH.

Amino Acid Sequence↗
PubMed1976

Studies on a protamine (galline) from fowl sperm. 4. Degradation of galline by trypsin-like protease of fowl sperm heads.

Galline, a protamine of domestic fowl, was obtained by two preparation procedures from the semen of a strain of White Plymouth Rock and submitted to fractionation by column chromatography on Bio-Gel CM-30. In the first procedure the specimen prepared from sperm heads was purified by the use of distilled water and dilute acetic acid and fractionated into almost eight fractions (G-I-G-VIII) in the same way as the specimen from a strain of New Hampshire (1,2). No difference could be found between galline specimens from the two different strains based on the amino acid and terminal analyses of each fraction. The specimen of galline from sperm heads purified with 1% citric acid (the second procedure) was composed of only one component, which was isolated as a single peak. The smaller fractions, G-I-G-VII, were found to be derived from G-VIII by the action of trypsin-like protease contained in the extract of sperm heads with 1% citric acid. This enzyme seems to originate in the acrosome of fowl spermatozoa. Consequently, it is concluded that intact galline is composed of only one molecular species and its total amino acid sequence is represented by the completed formula of G-VIII as shown in the preceding paper (4).

Amino Acid Sequence↗
PubMed1981

Endothelial surface charge: blood-brain barrier opening to horseradish peroxidase induced by the polycation protamin sulfate.

Perfusion of rat brain with the polycation protamin sulfate caused a decrease in the stainability of luminal surface of cerebral endothelium to positively charged colloidal iron. This change reflecting a decrease in the anionic sites of the endothelial plasma membrane was accompanied by opening of the blood-brain barrier to horseradish peroxidase. The polyanion heparin reversed colloidal iron binding but failed to prevent permeability alteration of the cerebral endothelium.

Animals↗
PubMed1983

Proteins of de-membraned protamine-depleted mouse sperm. Homology with proteins of somatic cell nuclear envelope/matrix.

Following treatment with Triton X/1 M NaCl/2-mercaptoethanol, mouse sperm heads are divested of protamines and other basic proteins; the residual structure is one in which the general morphological organization of the decondensed chromatin and the nuclear boundaries are conserved [1]. In this study, the protein complement of that residual structure has been characterized and subdivided into two sets: 1. Those that are sperm-unique, including constituents of the sperm head that may be intrinsically nuclear (or extra-nuclear, but exceedingly adherent to the nuclear envelope). 2. Those that display corresponding electrophoretic properties and immunologic cross-reactivity with proteins of similarly treated mouse somatic cell nuclei. Among the latter are proteins of molecular weight 52, 63 and 69 kD, two of which (63 and 69 kD) appear to be homologous to polypeptides of somatic nuclear envelope/pore complex lamina. Absence from sperm nuclei of the third of the characteristic predominant triplet of somatic nuclear lamina polypeptides of mammalian cells, here designated 67 kD, indicates cell-type variation in these structures. On the other hand, the identification of homologous polypeptides in the sperm and somatic complements suggests that those are specific instances of conservation and may represent the paternal contribution to the pool of polypeptides for assembly of the envelopes of the pronuclei of the one-cell embryo.

Animals↗
PubMed1990

Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats.

Absorption kinetics of regular, isophane (NPH), and protamine zinc (PZI) insulin were evaluated in seven clinically normal domestic shorthair cats by measurement of serial serum concentrations of insulin after subcutaneous administration of each insulin preparation. These results were compared to measurements of serial serum insulin concentrations after similar dosages of regular insulin were administered intravenously. Regular insulin administered subcutaneously was better absorbed than NPH and PZI insulins (mean bioavailability index 45.4% vs. 33.0% for NPH and 27.3% for PZI), and resulted in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (3529 pM vs. 1044 pM for NPH and 344 pM for PZI, P less than 0.05). The mean time interval between insulin administration and time to reach peak concentrations was significantly shorter for regular insulin than for NPH or PZI insulin (0.5 hr vs. 1.6 hr for NPH and 4.1 hr for PZI, P less than 0.05). There was also a significant difference (P less than 0.05) in the mean time interval between insulin injection and return of serum insulin concentrations to baseline values between regular insulin (5.6 hr) and NPH (7.7 hr) or PZI (13.1 hr) insulins. When compared with PZI, NPH insulin showed a significantly (P less than 0.05) greater maximal increase in mean serum insulin concentrations over baseline values. In addition, the interval between insulin administration and time to reach peak concentrations, as well as the time between insulin injection and return of serum insulin concentrations to baseline values, were also significantly shorter with NPH insulin than with PZI. These results suggest that NPH and PZI insulins administered subcutaneously to cats may require a short time to reach peak serum insulin concentrations as well as a relatively short time for circulating insulin concentrations to return to baseline values. If the absorption kinetics are similar to that in this study, most cats with diabetes mellitus would need twice daily injection of NPH or PZI insulin to adequately control the diabetic state.

Absorption↗
PubMed1999

Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens.

BACKGROUND: Neutral protamine Hagedorn (NPH) insulin is one of the most commonly used insulins in insulin pens. NPH in pen cartridges is in a two-phase solution with either a solvent or a short-acting insulin, and needs adequate mixing for complete resuspension. We assessed whether NPH insulin is accurately resuspended by patients and the association of suspension errors with diabetes control. METHODS: 109 patients (39 with type 1 diabetes) who had received conventional diabetic education had the NPH content of their cartridges measured by an optical system; a control cartridge was designated as 100%. A questionnaire was used to assess clinical details and insulin suspension habits. After the information about residual insulin error was known, all 109 patients were instructed to resuspend their insulin by rolling and tipping the pen 20 times. 52 patients were randomly selected to have cartridges re-analysed 3 months or 6 months later and to complete another questionnaire. FINDINGS: Only 10 (9%) of 109 patients tipped and rolled their pen more than ten times. NPH insulin content ranged from 5% to 214% and varied by more than 20% in 71 (65%) of 109 cartridges. There was no relation between inadequate suspension and the frequency of hypoglycaemic episodes (r=0.2, p=0.08). For all patients, there was a correlation between the absolute error of NPH suspension and cycles of rolling and tipping the pen (r=-0.23, p<0.05). After education on resuspending the pen's contents, data were available from 44 of 52 patients; suspension errors decreased in 35 (80%), were unchanged in three (7%), and increased in six (13%). The 35 patients with improved NPH insulin suspension had fewer mean hypoglycaemic episodes per month compared with the previous period (0.4 [SD 0.1] vs 1.0 [0.3], p<0.05). Mean HbA1c values in patients with improved suspension quality did not differ from baseline (8.4% [0.3] vs 8.9% [0.4], p=0.07). Mixing of NPH insulin by a mechanical device showed that at least 20 cycles were necessary before complete resuspension was obtained. INTERPRETATION: Inadequate NPH insulin suspension is common. We recommended that patients tip pens that contain NPH insulin at least 20 times, since inadequate mixing may impair diabetes control.

Adult↗
PubMed2004

Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen.

OBJECTIVE: The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn (NPH) insulin in basal-bolus therapy in combination with regular human insulin (HI) in patients with type 1 diabetes mellitus (DM). METHODS: This was a 6-month, prospective, randomized, open-label, controlled, parallel-group trial conducted at 92 sites in Europe and Australia. The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin (HbA(1c)) <== 12% already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin. Patients were randomly assigned (2:1) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals. Main outcome measures were blood glucose control as assessed by HbA(1c), fasting plasma glucose (FPG), 9-point self-monitored blood glucose (SMBG) profiles, 24-hour continuous blood glucose profiles, hypoglycemia, weight gain, and adverse events. RESULTS: Of the 749 patients randomized to treatment, 747 were exposed to trial products and included in the intent-to-treat analysis set. Seven hundred patients completed the trial: 465 (94.7%) in the insulin detemir group and 235 (91.8%) in the NPH group. After 6 months, FPG was lower with insulin detemir than with NPH (-1.16 mmol/L difference; P = 0.001), whereas HbA(1c) did not differ significantly between treatments (-0.12% [95% CI, -0.25 to 0.02]; P = NS). Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir (SD, 2.82 vs 3.60 mmol/L; P < 0.001). The overall shape of the 9-point SMBG profiles differed significantly between treatments (P = 0.006), with lower glucose levels before breakfast with insulin detemir than with NPH (P < 0.001). There was a 26% reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH (P = 0.003). Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH (-0.54 kg difference; P = 0.024). The frequency and type of adverse events were similar between treatment groups. CONCLUSIONS: In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets.

Adult↗
PubMed1986

[Comparison of the effects of protamine-bound NPH porcine insulin and NPH human insulin in type 1 and 2 diabetes].

Porcine and semisynthetic human insulin preparations (Nordisk) having the same content of regular insulin, same galenic characteristics and same degree of purity, were tested in type I, type IIa and type IIb diabetics. There was no difference as to the duration of action. This is contrary to some earlier reports stating that protamine-bound biosynthetic human insulin has a shorter duration of action than porcine preparations. The onset of the hypoglycaemic action in type IIa diabetics is significantly more rapid with isophane human insulin than with isophane pork insulin. The use of an insulin pump prior to testing the duration of action of intermediate insulin preparations appears to be superior to other methods.

Aged↗
PubMed2003

Reduced hypoglycemic episodes and improved glycemic control in children with type 1 diabetes using insulin glargine and neutral protamine Hagedorn insulin.

OBJECTIVE: The purpose of this study was to evaluate the use of a new long-acting basal insulin, insulin glargine (IG), in children with type 1 diabetes. Study design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60 girls), were collected for 9 months before and 9 months after IG treatment. During IG therapy, all subjects received morning neutral protamine Hagedorn insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage. The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values, body weight, and daily insulin dose were recorded at each clinic visit. RESULTS: The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced from a total of 22 in the 9 months before IG to nine in the 9 months after IG. Severe nocturnal events were similarly reduced from 14 to four episodes. The mean (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3 months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months (P=.01). CONCLUSION: Insulin glargine therapy can reduce hypoglycemic episodes in children and adolescents with suboptimal glucose control without jeopardizing glycemic control.

Adolescent↗
PubMed2004

A comparison of bedtime insulin glargine with bedtime neutral protamine hagedorn insulin in patients with type 2 diabetes: subgroup analysis of patients taking once-daily insulin in a multicenter, randomized, parallel group study.

BACKGROUND: Basal insulin is frequently administered once daily. This subgroup analysis of a multicenter, randomized, parallel study compared insulin glargine (Lantus Aventis Pharmaceuticals, Bridgewater, NJ) with neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes, evaluating only patients treated previously with once-daily NPH insulin. METHODS: Patients received bedtime insulin glargine or NPH insulin, with preprandial regular insulin. One hundred patients (mean age, 57.9 years; mean glycohemoglobin, 8.4%; mean fasting blood glucose, 167 mg/dL) were treated for up to 28 weeks. RESULTS: Patients treated with insulin glargine (n = 52) and NPH insulin (n = 48) achieved similar reductions from baseline in glycohemoglobin (-0.41% versus -0.46%) and fasting blood glucose (-22 mg/dL versus -22 mg/dL) at week 28. The proportion of patients reaching target fasting blood glucose (<120 mg/dL) at 28 weeks was 34.2% with insulin glargine and 24.4% with NPH insulin. Similar proportions of patients achieved glycohemoglobin less than 7% and less than 8% in both groups. Baseline and week-28 mean daily doses of insulin glargine (27.3 IU versus 36.4 IU) were similar to NPH insulin doses (25.5 IU versus 30.2 IU). However, significantly fewer patients reported one or more episodes of hypoglycemia with insulin glargine (46.2%) versus NPH insulin (60.4%; P < 0.05). Significantly fewer patients also reported one or more symptomatic episodes confirmed by blood glucose less than 50 mg/dL with insulin glargine (17.3%) versus NPH insulin (31.3%; P < 0.005). CONCLUSION: Bedtime insulin glargine is as effective as bedtime NPH insulin in improving glycemic control, with significantly less hypoglycemia.

Body Mass Index↗
PubMed2005

Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy.

AIM: To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients. METHODS: Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L. RESULTS: Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02). CONCLUSION: Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.

Adolescent↗
PubMed1965

Defibrination syndrome with defective thrombinfibrinogen reaction reversible by protamine.

A patient with the obstetric defibrination syndrome successfully treated with human fibrinogen is described. The blood not only contained low levels of fibrinogen capable of clotting but also contained an inhibitor of the thrombin-fibrinogen reaction. This was neutralized in vitro with protamine but it was not heparin. Neither abnormality was detected by a latex agglutination test for plasma fibrinogen. The use of this test does not therefore exclude the diagnosis of the defibrination syndrome.

Adult↗
PubMed1996

Pulmonary responses to heparin-protamine complexes: the effects of age and species.

To test the hypothesis that heparin-protamine complexes (H-P complexes) react with pulmonary intravascular macrophages, we studied the difference in the pulmonary reaction to H-P complexes between goats and rabbits and among different-aged goats. The increases in pulmonary arterial pressure (Ppa) and plasma thromboxane levels (Tx) after injection of H-P complexes (1.2 ml/kg) in goats (delta Ppa = 17 +/- 7.0 mmHg, delta Tx = 17.3 +/- 10.1 ng/ml) were significantly greater than in rabbits (delta Ppa = 0.50 +/- 1.0 mmHg, delta Tx = -0.01 +/- 0.17 ng/ml), the increase in Ppa in adult goats (> 150 days old; delta Ppa = 17 +/- 7.0 mmHg) was about sixfold higher than in newborn goats (1-3 days old; delta Ppa = 2.8 +/- 4.0 mmHg), and the increase in Tx in adult goats (delta Tx = 17.3 +/- 10.1 ng/ml) was significantly greater than those in newborn and young (19 days old) goats (delta Tx = 0.69 +/- 0.48 and 3.60 +/- 0.36 ng/ml, respectively). The pulmonary hemodynamic reaction to H-P complexes is consistent with the concept that the H-P complexes react with pulmonary intravascular macrophages.

Aging↗
PubMed2001

Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats.

OBJECTIVE: To evaluate effects of protamine zinc insulin (PZI) on control of glycemia in cats with newly diagnosed diabetes mellitus or poorly controlled diabetes. DESIGN: Clinical trial. ANIMALS: 67 diabetic cats. PROCEDURE: 34 cats with newly diagnosed diabetes and 33 cats with poorly controlled diabetes were treated with PZI twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of clinical response, change in body weight, serum fructosamine concentration, blood glucose concentration measured 1, 3, 5, 7, and 9 hours after administration of PZI, lowest blood glucose concentration, and mean blood glucose concentration during the 9-hour period after administration. Adjustments in dosage of PZI were made as needed to attain control of glycemia. RESULTS: For all cats, a significant increase in mean dosage of PZI and significant decreases in 9-hour mean blood glucose concentration, lowest mean blood glucose concentration, and mean serum fructosamine concentration were detected. For cats with poorly controlled diabetes, 9-hour mean blood glucose concentration and mean serum fructosamine concentration were significantly decreased on day 45, compared with day 0. Ninety percent of owners reported improvement or resolution of clinical signs by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PZI was effective for control of glycemia in cats with newly diagnosed or poorly controlled diabetes and may be used as an initial treatment or as an alternative treatment in cats that do not respond to treatment with other types of insulin.

Animals↗
PubMed2002

Administration of neutral protamine Hagedorn insulin at bedtime versus with dinner in type 1 diabetes mellitus to avoid nocturnal hypoglycemia and improve control. A randomized, controlled trial.

BACKGROUND: Intensive insulin treatment of type 1 diabetes mellitus increases the risk for nocturnal hypoglycemia. OBJECTIVE: To demonstrate that splitting the evening insulin regimen reduces the risk for nocturnal hypoglycemia in intensive treatment of type 1 diabetes mellitus. DESIGN: Randomized, open, two-treatment crossover trial in two 4-month periods. SETTING: University research center in Italy. PATIENTS: 22 C-peptide-negative persons with type 1 diabetes mellitus (mean age [+/-SD], 29 +/- 3 years). INTERVENTIONS: Each patient was randomly assigned to one of two insulin regimens for 4 months and then switched to the other regimen for another 4 months. The two treatment regimens were 1) mixed treatment--a mixture of human regular and neutral protamine Hagedorn (NPH) insulin administered before dinner and 2) split treatment--human regular insulin administered at dinner and NPH insulin administered at bedtime. MEASUREMENTS: Frequency of nocturnal hypoglycemia. Secondary end points were levels of fasting blood glucose and hemoglobin A1c and responses to experimental hypoglycemia. RESULTS: During the split-regimen treatment period, patients had fewer episodes of nocturnal hypoglycemia (mean [+/-SE], 0.10 +/- 0.02 episode/patient-day vs. 0.28 +/- 0.04 episode/patient-day; P = 0.002), a lower fasting blood glucose level (mean [+/-SE], 7.6 +/- 0.2 mmol/L vs. 8.3 +/- 0.5 mmol/L [137 +/- 4 mg/dL vs. 160 +/- 8 mg/dL]; P = 0.030), less variable fasting blood glucose levels (SD range, 2.0 +/- 0.4 vs. 3.5 +/- 0.6; P = 0.001), and lower hemoglobin A1c value (mean [+/-SE], 7.0% +/- 0.11% vs. 7.5% +/- 0.15%; P = 0.004) than during the mixed regimen. Responses to experimental hypoglycemia were better preserved with the split regimen than with the mixed regimen. CONCLUSION: When the goal of insulin therapy in type 1 diabetes mellitus is near-normoglycemia, splitting the evening insulin treatment regimen into short-acting insulin at dinner and NPH insulin at bedtime reduces the risks for nocturnal hypoglycemia and hypoglycemia unawareness and decreases the hemoglobin A1c value compared with mixing short-acting insulin and NPH insulin at dinner.

Adult↗
PubMed2003

Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.

BACKGROUND: Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin. OBJECTIVE: To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. DESIGN: Open-label, randomized, controlled trial. SETTING: 111 centers in 13 European countries. PATIENTS: 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents. INTERVENTION: Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL). MEASUREMENTS: Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight. RESULTS: Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P < 0.001). CONCLUSION: The risk for nocturnal hypoglycemia was lower with glimepiride in combination with morning and bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.

Aged↗