A randomized controlled trial of Sweet Talk, a text-messaging system to support young people with diabetes.

AIMS: To assess Sweet Talk, a text-messaging support system designed to enhance self-efficacy, facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes. METHODS: One hundred and twenty-six patients fulfilled the eligibility criteria; Type 1 diabetes for > 1 year, on conventional insulin therapy, aged 8-18 years. Ninety-two patients were randomized to conventional insulin therapy (n = 28), conventional therapy and Sweet Talk (n = 33) or intensive insulin therapy and Sweet Talk (n = 31). Goal-setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system, containing personalized goal-specific prompts and messages tailored to patients' age, sex and insulin regimen. RESULTS: HbA(1c) did not change in patients on conventional therapy without or with Sweet Talk (10.3 +/- 1.7 vs. 10.1 +/- 1.7%), but improved in patients randomized to intensive therapy and Sweet Talk (9.2 +/- 2.2%, 95% CI -1.9, -0.5, P < 0.001). Sweet Talk was associated with improvement in diabetes self-efficacy (conventional therapy 56.0 +/- 13.7, conventional therapy plus Sweet Talk 62.1 +/- 6.6, 95% CI +2.6, +7.5, P = 0.003) and self-reported adherence (conventional therapy 70.4 +/- 20.0, conventional therapy plus Sweet Talk 77.2 +/- 16.1, 95% CI +0.4, +17.4, P = 0.042). When surveyed, 82% of patients felt that Sweet Talk had improved their diabetes self-management and 90% wanted to continue receiving messages. CONCLUSIONS: Sweet Talk was associated with improved self-efficacy and adherence; engaging a classically difficult to reach group of young people. While Sweet Talk alone did not improve glycaemic control, it may have had a role in supporting the introduction of intensive insulin therapy. Scheduled, tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care settings and chronic diseases.     

Short-term effects of cognitive behavioural group training (CBGT) in adult Type 1 diabetes patients in prolonged poor glycaemic control. A randomized controlled trial.

AIMS: To assess the effects of cognitive behavioural group training (CBGT) on glycaemic control, diabetes self-efficacy and well-being in Type 1 diabetes patients in persistent poor glycaemic control. METHODS: In a randomized controlled trial, a total of 107 patients with Type 1 diabetes in poor glycaemic control (HbA(1c) > or = 8%) were assigned to a 6-week CBGT or blood glucose awareness training (BGAT) as control condition. The intervention was preceded by a 3-month run-in period. Glycaemic control (HbA(1c)), diabetes-specific self-efficacy (CIDS), diabetes-related distress (PAID) and depressive symptoms (CES-D), were assessed at baseline (T1), directly before (T2) and 3 months after (T3) the intervention. RESULTS: No significant changes in HbA(1c) were found after CBGT, whilst diabetes self-efficacy increased (mean CIDS score 71.6 +/- 14.0 to 74.3 +/- 12.2) and diabetes-related distress (mean PAID score 47.0 +/- 21.6 to 42.6 +/- 20.8) and depressive symptoms decreased (mean CES-D score 16.9 +/- 12.8 to 13.5 +/- 12.6). Changes in psychological outcomes were similar for both treatment groups. Diabetes self-care behaviours improved equally. Drop-out rate, which was higher among CBGT participants, was relatively low overall (total n = 15, 17.05%), and both interventions were well-appreciated by the participants. CONCLUSIONS: CBGT was successful in improving self-efficacy, diabetes-related distress and mood at 3 months' follow-up, but not in improving glycaemic control.     

Determinants of adiponectin levels in young people with Type 1 diabetes

Aims To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non‐diabetic controls, and explore potential determinants for this difference. Methods Data are from the SEARCH for Diabetes in Youth Case‐Control Study. A total of 440 youth with Type 1 diabetes and 191 non‐diabetic healthy controls age 10–22 years of non‐Hispanic White (NHW), African‐American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA_1c). Results Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 µg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA_1c in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity. Conclusions Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.     

Family conflict, adherence, and glycaemic control in youth with short duration Type 1 diabetes.

AIMS: Behavioural support around diabetes management tasks is linked to glycaemic outcomes. In this study we investigated the relationship between diabetes-related parental behaviours (conflict around and involvement in treatment tasks), adherence to blood glucose monitoring (BGM), and glycaemic control in youth with short duration Type 1 diabetes mellitus (DM). METHODS: In a cross-sectional study, 104 youth (aged 8-17 years, duration of Type 1 DM 0.5-6 years) along with a parent, completed the Diabetes Conflict Scale. Parental involvement in management tasks was assessed with structured interviews and the Diabetes Family Responsibility Questionnaire. Adherence to BGM was evaluated by family report and by independent clinician rating. Glycaemic control was assessed with glycosylated haemoglobin (HbA1c) (ref. range, 4-6%). RESULTS: Children (8-12 years; n = 69) and adolescents (13-17 years; n = 35), respectively, had similar durations of diabetes (x +/- sd; 2.7 +/- 1.69, 2.4 +/- 1.32 years) and similar glycaemic control (8.3 +/- 1.1%, 8.4 +/- 1.1%). In both age groups, parental involvement was a significant predictor of adherence to BGM (P = 0.01). Multivariate analyses, controlling for age, sex, disease duration, and BGM adherence, revealed that higher diabetes conflict significantly related to poorer glycaemic control (HbA1c) (R2 = 0.17; P < 0.01). CONCLUSIONS: These findings indicate that in this cohort, early in the course of diabetes, diabetes-specific conflict and adherence to BGM became strongly linked to the child's glycaemic control. This suggests that to insure optimal control, it may be beneficial to introduce targeted interventions to build positive family involvement and interaction around diabetes tasks early in the disease course, before negative behaviours become established.     

A randomized trial of insulin aspart with intensified basal NPH insulin supplementation in people with Type 1 diabetes.

AIMS: Insulin aspart has been shown to improve post-prandial and overall glycaemic control in people with Type 1 diabetes. We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with standard basal NPH insulin. METHODS: The trial was conducted in 43 centres in seven countries. People with Type 1 diabetes were randomized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25% increase in bedtime NPH dose (n = 187), or to mealtime human unmodified insulin with once or twice daily basal NPH insulin (n = 181). Efficacy and safety were evaluated at 12 weeks (primary evaluation period) and 64 weeks. RESULTS: At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups: -0.09 (95% confidence interval (CI) -0.23, +0.05)% and -0.14 (-0.32, +0.04)%. Post-prandial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28% smaller with insulin aspart (35.2 +/- 3.2 vs. 48.9 +/- 3.1 mmol/l h, P = 0.0015). No significant differences were found in mild or severe hypoglycaemia, or adverse event rate. At 64 weeks treatment satisfaction was higher in the insulin aspart group (difference 1.57 (95% CI 0.49, 2.64) points, P = 0.004), while quality of life was not different. CONCLUSIONS: Improved post-prandial glycaemic control and treatment satisfaction with insulin aspart were confirmed. Intensifying basal insulin supplementation resulted in a similar HbA1c decrement as previously found with the use of insulin aspart and standard NPH insulin supplementation. This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice.     

Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes.

AIMS: To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. METHODS: In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. RESULTS: HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). CONCLUSIONS: Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.     

Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes.

AIMS: To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes. METHODS: This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30-45 mg/day or gliclazide 80-320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA1c values. The 1-year changes in HbA1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques. RESULTS: In both groups, there were similar decreases in HbA1c (pioglitazone: -0.79%; gliclazide: -0.79%) and FBG (pioglitazone: -1.0 mmol/l; gliclazide: -0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (-11.94 pmol/l and -1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (-2.48 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups. CONCLUSIONS: A comparable decrease in HbA1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.     

Persistent poor glycaemic control in adult Type 1 diabetes. A closer look at the problem.

Around 25% of the adult Type 1 diabetes population is in persistent poor glycaemic control and thus at increased risk of developing microvascular complications. We here discuss correlates of long-standing poor glycaemic control and review the efficacy of clinical strategies designed to overcome persistent poor control. Only a few studies have identified determinants and correlates of long-standing poor glycaemic control in Type 1 diabetes. There is some evidence implicating genetic factors, as well as lower economic status, and psychological factors, including lack of motivation, emotional distress, depression and eating disorders. Ways of improving glycaemic control include strategies to enable self-management, e.g. motivational strategies, coping-orientated education, psychosocial therapies, and/or intensifying insulin injection therapy plus continuous subcutaneous insulin infusion. Long-standing poor glycaemic control appears to be a heterogeneous and complex phenomenon, for which there is no simple, single solution. Comprehensive psycho-medical assessment in diabetes care may prove useful in tailoring interventions. Further research is warranted, to increase our understanding how psychosocial and biomedical factors, separately and in interaction, determine poor outcomes in Type 1 diabetes.     

Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood.

AIMS: After Danish nationwide investigations (1987, 1989) demonstrated unacceptable blood glucose control in unselected young diabetic patients, we set out to estimate the present glycaemic control and the prevalence of microvascular complications in a cohort of children and adolescents participating in the two previous studies. METHODS: This follow-up represents 339 patients (47% of the inception cohort), median age 21.1 years (range 12.0-26.9), median diabetes duration 13.2 years (range 8.9-24.5). A standardized questionnaire, fundus photographs (with central reading) and a physical examination were performed. HbA1c and overnight albumin excretion rate (AER) were analysed centrally. RESULTS: Although 88% (n= 309) of the young persons were treated with three or more daily insulin injections, HbA1c (nondiabetic range 4.3-5.8, mean 5.3%) was 9.7+/-1.7% (mean+/-SD). Males had higher HbA1c values than females (P < 0.015). Mean daily insulin dose was 0.92+/-0.25 IU.kg(-1).24h(-1). Microalbuminuria (AER > 20-150 microg/min) and macroalbuminuria (AER > 150 microg/min) were found in 9.0% and 3.7% of the patients, respectively, and was associated with increased diastolic blood pressure (P<0.01) and presence of retinopathy (P<0.01). Retinopathy was present in approximately 60% of the patients and was associated with age, diabetes duration, HbA1c, diastolic blood pressure and AER (all P<0.01). Subclinical neuropathy (vibration perception threshold by biothesiometry > 6.5 V) was found in 62% and showed a significant association with age, linear height, diastolic blood pressure (all P < 0.01) and diabetic retinopathy (P = 0.01). CONCLUSIONS: In spite of the majority of the patients being on multiple insulin injections, only 11% had HbA1c values below 8% and the prevalence of diabetic microvascular complications in kidneys, eyes and nerves was unacceptable high.     

Child and parental mental ability and glycaemic control in children with Type 1 diabetes.

AIMS: Many psycho-social factors can affect the glycaemic control of children with Type 1 diabetes, but the influence of the intelligence of the child and their parents has not been reported. METHODS: Seventy-eight children and adolescents with Type 1 diabetes and their mothers performed standardized tests to assess psychometric intelligence. The children were aged (median (range)) 12.0 (5-17) years with duration of diabetes 5.0 (1.0-13.0) years and required an insulin dose of (mean +/- SD) 1.0 +/- 0.3 U/kg per day. The children completed the Wide Range Achievement Test 3 reading test (WRAT3) and Raven's Standard Progressive Matrices (RSPM). A mean annual HbA1c was calculated for each subject (8.6 +/- 1.4%). The mothers performed the National Adult Reading Test (NART) and provided details of the occupation of the main wage-earner in the family from which social class (SC) was derived. RESULTS: The HbA1c of the child correlated with their age (r = 0.26, P = 0.02), SC (Kendall's rank correlation, tau = 0.17, P = 0.03) and with the NART error score of their mother (r = 0.28, P = 0.01), but no correlation was observed with the child's WRAT3 or RSPM score. Stepwise regression revealed that age and NART error score were the strongest independent determinants of glycaemic control (total adjusted r2 = 0.117). CONCLUSIONS: Parental intelligence appears to have a significant influence on the glycaemic control of a child with Type 1 diabetes, accounting for 7.6% of the reliable variance in HbA1c.     

Clinical effectiveness of a brief educational intervention in Type 1 diabetes: results from the BITES (Brief Intervention in Type 1 diabetes,Education for Self‐efficacy) trial

Aims Intensive 5‐day educational interventions for people with Type 1 diabetes have shown improved outcomes in a number of European studies. The aim was to assess the effectiveness of a brief (2.5 days) psycho‐educational intervention. Methods Our randomized trial in a secondary‐care setting had 54 and 60 participants allocated to intervention and control groups, respectively. Primary outcomes were HbA_1c and severe hypoglycaemia. Secondary outcomes were blood pressure, weight, height, lipids and psychometric profile. Results HbA_1c showed no statistically significant change at 3 months [difference = 0.01, 95% confidence interval (CI) –0.23, 0.26, P = 0.92], 6 months (difference = –0.06, 95% CI –0.32, 0.20, P = 0.67) and 12 months (difference = 0.01, 95% CI –0.30, 0.32, P = 0.94). Incidence of severe hypoglycaemia (per patient per year) in the intervention group (0.41) and control group (0.48) was not statistically different. Treatment satisfaction improved at 3 months (difference = 9.4, 95% CI 5.2, 13.6, P = 0.0005), 6 months (difference = 10.4, 95% CI 6.0, 14.8, P = 0.0005) and 12 months (difference = 7.1, 95% CI 2.1, 12.1, P = 0.006). The ‘Managing psychological aspects’ and ‘Setting and achieving goals’ dimensions of the Diabetes Empowerment Scale also showed significant improvement at 3, 6 and 12 months. Diabetes Knowledge Test, Illness Perception Questionnaire, Hypoglycaemia Fear Scale and Short Form 36 showed no significant change. Conclusions This brief intervention had no significant impact on HbA_1c or severe hypoglycaemia, but improved diabetes treatment satisfaction and patient empowerment. Current Controlled Trials ISRCTN75807800.     

A longitudinal observational study of insulin therapy and glycaemic control in Scottish children with Type 1 diabetes: DIABAUD 3

Objective/background Our objective was to investigate glycaemic control in children with Type 1 diabetes in Scotland and to analyse the effect of changing ‘conventional’ insulin regimen strategies on outcome. DIABAUD  2 (1997–1998) (D2) demonstrated that average glycaemic control in young people with Type 1 diabetes in Scotland was poor, with mean HbA_1c of 9.0%. Over 90% were then treated with a twice‐daily insulin regimen. The aim of DIABAUD  3 (2002–2004) (D3) was to determine if control had improved, and to examine changes in insulin regimen and effects on glycaemic control. Methods In DIABAUD  3, data were collected prospectively on children aged < 15 years. in nine out of 15 centres throughout Scotland. HbA_1c on 986 subjects was measured in a single Diabetes Control and Complications Trial‐aligned laboratory. The results were compared with those from DIABAUD  2, for the same nine centres. Multiple regression comparison was performed to adjust for imbalance in relevant confounders (e.g. age, duration, height and weight, insulin dose and centre). Results For D3, the age range was 1.1–14.9 years (62% aged 10–14 years), mean (± sd ) HbA_1c 9.2% ± 1.5 (compared with D2, 9.0% ± 1.5). Only 9.7% achieved the target of HbA_1c < 7.5%. The number of subjects in D3 on twice‐daily injections was 51% (compared with 94% in D2), 43% on three‐times‐daily injections (2% in D2) and 2.3% on four or more (1.9% in D2): HbA_1c did not differ in these groups. In both the D2 and D3 cohorts, HbA_1c rose with age. After adjustment for other variables in the combined datasets, insulin regimen was not a significant predictor of HbA_1c (F = 0.19, d.f. = 3, 1774; P = 0.90). Conclusion The glycaemic control in young people in Scotland remains poor and above the national target. Over 4 years, moderate intensification of insulin therapy (i.e. from two to three injections each day, usually reflecting splitting of the evening dose) across the population failed to improve the average HbA_1c and reduce the increase seen with age. A national programme away from ‘conventional’ to an ‘intensive’ regimen of insulin therapy is required.     

Glycaemic control and body mass index in late‐adolescents and young adults with Type 1 diabetes mellitus: a population‐based study

Aims Studies of children with diabetes up to the age of 15 years report deteriorating glycaemic control in the early teenage years. The aim was to investigate glycaemia and body mass index in older teenagers and young adults. Method A Scottish, regional, population‐based, cross‐sectional study of 255 young people (117 female, 138 male) with Type 1 diabetes, aged 15–25 years (mean ±sd 19.8 ± 2.8 years, diabetes duration: 8.8 ± 5.4 years) registered on a diabetes database. Glycaemic control, body mass index (BMI) and insulin regimens were assessed in three age groups [group 1 (n = 96) 15–18 years; group 2 (n = 74) 18.1–22 years; and group 3 (n = 85) 22.1–25 years]. Results Subjects in the oldest age group had a significantly lower mean HbA_1c than those in the youngest age group (8.8 ± 1.7 vs. 9.9 ± 1.9%; P < 0.001). Mean BMI was higher in group 3 (25.2 ± 3.4 kg/m²) compared with group 1 (23.9 ± 3.1 kg/m²; P < 0.001). HbA_1c levels were higher in the younger subjects and women. Lower HbA_1c levels were associated with a higher BMI (r = ?0.324, P < 0.001) in men only. Overall, 74% took three or more injections a day, of whom 60% were on basal/bolus therapy. The proportion on basal/bolus insulin therapy increased with age and duration of diabetes. Conclusion Compared with adolescents, young adults with Type 1 diabetes have better glycaemic control and higher BMI. This was associated with lower insulin requirements.     

The effect of model-based telephone counseling on HbA1c and self-management for individuals with type 2 diabetes: A randomized controlled trial

AimsThis study was conducted to examine the effect of telephone counseling based on the Information, Motivation, Behavioral Skills (IMB) Model on HbA1c and self-management in patients with type 2 diabetes mellitus (T2DM).MethodsThis study was conducted between January 2019 and September 2019 with a total of 63 (31 interventions, 32 controls) T2DM patients. The intervention group was followed-up for a total of 12 weeks, after 45?60 min of patient training based on IMB, a weekly reminder message and a phone call every two weeks. No intervention was made to the control group. Data were collected at the beginning of the study and at the end of the 12th week. The data were obtained using a Patient Information Form, the Type 2 Diabetes Self-Efficacy Scale, the Diabetes Self-Management Questionnaire (DSMQ), the Perceived Diabetes Self Management Scale (PDSMS) and glycemic control (HbA1c).ResultsParticipants were on average 54 years old and the majority were female (58.1%). According to the results of the covariance analysis (ANCOVA), there was a statistically significant difference between the pre-post-test HbA1c (F:13.589; p < 0.001), weight (F:32.176; p < 0.001) and systolic blood pressure (F:7.109; p = 0.01). However, there was no significant difference in diastolic blood pressure between the intervention and control groups (F:2.686; p = 0.106). Also, after three months of follow-up, self-efficacy (F:26.632; p < 0.001), self-management (F:44.487; p < 0.001) and self-management perceptions (F:71.132; p < 0.001) were significantly higher in the intervention group.ConclusionThe researchers concluded that telephone counseling based on the IMB model could be a suitable method to improve glycemic control and self-care behaviors in patients with type 2 diabetes.     

Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trial.

OBJECTIVE: To determine the effect of adding nateglinide to therapy with insulin glargine in adults with Type 2 diabetes previously treated with insulin and with poor blood glucose control. RESEARCH DESIGN AND METHODS: In this 16-week, double-blind, placebo-controlled study, people with Type 2 diabetes [n = 55, HbA(1c) 8.2 +/- 1.0 (+/- sd)%, duration of diabetes 12.8 +/- 6.0 years, duration of insulin treatment 6.0 +/- 4.0 years] were transferred to single bedtime injection of insulin glargine for a titration period of 4 weeks, and then randomized to nateglinide or matching placebo before meals in addition to insulin glargine. Metformin was continued if taken. Doses of insulin and oral medication were titrated to protocol for the treatment period of 12 weeks. RESULTS: Baseline-adjusted self-monitored capillary blood glucose concentration at 12 weeks was significantly lower with nateglinide + insulin glargine compared with placebo + insulin glargine after breakfast [difference -2.3 (95% confidence interval -4.4, -0.2) mmol/l, P = 0.030], before lunch [-2.5 (-4.6, -0.3) mmol/l, P = 0.029], and after lunch [-2.3 (-4.3, -0.4) mmol/l, P = 0.021], but not at other times. Baseline-adjusted HbA(1c) was not lower with nateglinide + insulin glargine as compared with placebo + insulin glargine [7.8 +/- 1.4 vs. 8.3 +/- 1.0%, difference -0.43 (-0.98, 0.12)%]. CONCLUSIONS: Addition of nateglinide before meals to once-daily insulin glargine in people with long-standing diabetes already requiring insulin therapy improves blood glucose control in the early part of the day after breakfast and lunch, but does not provide good control of blood glucose levels overall.