Frequency and Symptoms of Hypoglycaemia Experienced by Patients with Type 2 Diabetes Treated with Insulin

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1–17) years (median (range)) vs partial awareness: 9 (3–18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2–25) years vs partial awareness: 19 (8–24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1–18) years vs partial awareness: 12 (6–17) years, p < 0.001). Severe hypoglycaemia in the preceding year had occurred with a similar prevalence in the Type 2 patients (9 (10%)) and Type 1 patients (14 (16%)), but was more frequent in those patients with partial awareness both in Type 1 patients (normal awareness: 3 (4%) vs partial awareness: 11 (73%), p < 0.001) and in Type 2 patients (normal awareness: 3 (4%) vs partial awareness: 6 (100%), p < 0.001). Although the symptoms of hypoglycaemia were idiosyncratic in individual Type 2 patients, the range and prevalence of specific symptoms were similar to those described by the patients with Type 1 diabetes.     

Flexible,intensive insulin therapy and dietary freedom in adolescents and young adults with Type 1 diabetes: a prospective implementation study

Aims To assess the outcome of a Diabetes Treatment and Teaching Programme (DTTP) on glycated haemoglobin (HbA_1c), severe hypoglycaemia (SH) and severe ketoacidosis (SKA) in adolescents and young adults with Type 1 diabetes. Methods Quality-assurance project with assessment of participants 1 year after participation in a DTTP (5-day inpatient course, groups ≤ 10 patients, fixed curriculum of education/training, introduction of dietary freedom). Before–after analyses of participants aged 12–15, 15–18, 18–21 and 21–24 years. Main outcome measures were HbA_1c, SH and SKA. Results For the 1592 participants, aged 12 to 24 years, mean age at enrolment was 19 ± 3 years, mean duration of diabetes was 7.3 ± 5.4 (range 0.3–24) years, mean baseline HbA_1c declined from 8.8 ± 2.3% to 8.1 ± 2.0%. The incidence of SH was 0.31 vs. 0.11 events/patient/year; the incidence of SKA 0.17 vs. 0.07 events/patient/year. In mixed effects models taking into account effects of centres, age and diabetes duration, the mean difference was −0.64%[P < 0.001, 95% confidence interval (CI) −0.79 to −0.5] for HbA_1c, −0.2 events/patient/year (P < 0.0001, 95% CI −0.28 to −0.12) for SH and −0.1 events/patient/year (P < 0.0001, 95% CI −0.14 to −0.06) for SKA. Conclusions Adolescents and young adults with Type 1 diabetes benefit from participation in a standard DTTP for flexible, intensive insulin therapy and dietary freedom.     

Short‐term nocturnal hypoglycaemia increases morning food intake in healthy humans

Aims Hypoglycaemia during wakefulness increases hunger and food intake. Patients with Type 1 diabetes mellitus are at high risk of recurrent hypoglycaemia and weight gain. Given the background of frequent hypoglycaemic episodes during night‐time sleep in diabetic patients, we investigated morning food intake after nocturnal hypoglycaemia. Methods We tested 16 healthy normal‐weight subjects (eight women) on three nights. A linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion immediately after sleep onset (‘early hypo’) or after about 3.5 h of sleep (‘late hypo’). On a control night, no hypoglycaemia was induced. Spontaneous food intake at a breakfast buffet was registered on the subsequent morning. Results Compared with the control condition (700 ± 93 kcal), subjects ate more after ‘late hypo’ (867 ± 108 kcal; P = 0.041), but not after ‘early hypo’ (852 ± 111 kcal; P = 0.130). Analyses of macronutrient fractions revealed that in comparison with the control condition, subjects ate significantly more carbohydrates after both ‘late hypo’ (277 ± 25 kcal vs. 206 ± 23 kcal, P < 0.001) and ‘early hypo’ (245 ± 23 kcal, P = 0.048), with this effect being more pronounced after late than early nocturnal hypoglycaemia (P = 0.026). Conclusions In healthy subjects, nocturnal hypoglycaemia during sleep stimulates spontaneous food intake the following morning, with carbohydrate intake being especially affected. Effects were more pronounced after ‘late hypo’, suggesting the influence of temporal dynamics. Although healthy non‐diabetic subjects were studied, similar mechanisms may contribute to the frequently observed body weight gain in insulin‐treated diabetic patients.     

Hypoglycaemia in insulin-treated Type 2 diabetes: frequency,symptoms and impaired awareness

Aims Hypoglycaemia is considered to be less common in people with insulin-treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin-treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced. Methods The frequencies of mild (self-treated) and severe (required assistance) hypoglycaemia during the preceding year were estimated retrospectively. The usual symptoms of hypoglycaemia and state of awareness of hypoglycaemia were scored using validated questionnaires and any history suggestive of impaired hypoglycaemia awareness was documented. Results In this cohort, 157 (73%) had experienced hypoglycaemia since commencing insulin, the frequency of which increased with duration of diabetes and of insulin therapy and was inversely related to current HbA_1c (all P < 0.05). During the preceding year, 32 individuals (15%) had experienced severe hypoglycaemia, with an estimated incidence for the entire group of 0.28 episodes/patient/year. Principal components analysis revealed two underlying symptom groups (autonomic and neuroglycopenic), similar to those reported previously by young adults with Type 1 diabetes, but the total symptom score declined with advancing age. Of the 157 with a history of hypoglycaemia, the 13 (8%) individuals who gave a history of impaired awareness of hypoglycaemia had experienced a ninefold higher incidence of severe hypoglycaemia than those with normal awareness, and reported experiencing mainly neuroglycopenic symptoms. Conclusions While the overall frequencies of mild and severe hypoglycaemia were lower in insulin-treated Type 2 diabetes than have been reported previously in Type 1 diabetes, the risk of hypoglycaemia was greater with increasing duration of diabetes and of insulin therapy. Although impaired awareness of hypoglycaemia was uncommon, it was associated with a higher incidence of severe hypoglycaemia. Diabet. Med. 20, ***–*** (2003)     

Glycaemic profile characteristics and frequency of impaired awareness of hypoglycaemia in subjects with T1D and repeated hypoglycaemic events

The aim of our study was to evaluate the frequency of hypoglycaemia unawareness and the continuous glucose profile in a group of subjects with Type 1 diabetes (T1D) with repeated non-severe/severe hypoglycaemia. Twenty patients (aged 35.2 ± 7.6 years, duration of disease 16.4 ± 6.4 years) were included. Hypoglycaemia awareness was evaluated using questionnaires and after an acute-induced hypoglycaemia. Glucose profile was studied using 72-h continuous glucose monitoring (CGM). All subjects were classified as having hypoglycaemia unawareness by questionnaires. Four patients displayed a “normal” signs/symptoms response to hypoglycaemia. The CGM revealed 18% of the measurements <70 mg/dl and this percentage was correlated with questionnaire score (r = 0.55, P < 0.035) and with the increase in the percentage of signs/symptoms during the induced hypoglycaemia (r = −0.57, P < 0.015). In patients exhibiting an “abnormal” response during hypoglycaemia, CGM values <70 mg/dl was higher (22.6 ± 8.4%) than in those with a “normal” response (10.2 ± 9.0%; P < 0.028). Summarising, in subjects with T1D and repeated hypoglycaemia the frequency of impaired awareness is substantially common. Its presence is related to a high proportion of ambulatory glycaemic profile below the desirable range.     

Is autonomic neuropathy a risk factor for severe hypoglycaemia? The EURODIAB IDDM Complications Study

Summary The hypothesis that diabetic patients with autonomic neuropathy are at increased risk of severe hypoglycaemia was examined in an epidemiological study of over 3000 IDDM patients in Europe (EURODIAB IDDM Complications Study). Autonomic function was assessed by two standard cardiovascular tests: change in heart rate and systolic blood pressure on standing. Severe hypoglycaemia was defined as an attack serious enough to require the help of another person. Compared to patients (68 %) reporting no attacks in the last year, those reporting one or more attacks were older (34.0 ± 10.7 vs 32.1 ± 9.9 years, mean ± SD, p < 0.0001), had had diabetes for a longer period (16.6 ± 9.5 vs 13.8 ± 9.1 years, p < 0.0001), had better glycaemic control (HbA_1c 6.4 ± 1.8 vs 6.9 ± 1.9 %, p < 0.0001) and were more likely (p = 0.002) to have abnormal responses to both autonomic tests (13.0 vs 7.7 %). A single abnormal autonomic response was not associated with an increased risk of severe hypoglycaemia. The odds ratio for severe hypoglycaemia in people with abnormal responses to both autonomic tests, compared to those with normal responses, was 1.7 (95 % confidence interval 1.3, 2.2) after controlling for age, duration of diabetes, glycaemic control and study centre. In conclusion, a combined autonomic deficit in heart rate and blood pressure responses to standing is associated with only a modest increase in the risk of severe spontaneous hypoglycaemia. Although the increase in risk is not large, severe hypoglycaemia was a frequently reported event in this study. IDDM patients with deficient autonomic responses who strive for tight glycaemic control may therefore be at particular risk of severe hypoglycaemia. [Diabetologia (1996) 39: 1372–1376] Received: 28 December 1995 and in final revised form: 11 June 1996     

Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics

Aim

To investigate severe hypoglycaemia (SH) in adults with type 1 diabetes and its associations with impaired awareness of hypoglycaemia (IAH), clinical, psychological and socio-demographic factors.

Methods

Attendees of three specialist diabetes clinics in Melbourne, Australia completed questions about frequency of SH in the past six months; impaired awareness of hypoglycaemia (Gold score); and measures of general emotional well-being (WHO-5), diabetes-specific positive well-being (subscale of W-BQ28), diabetes-related distress (PAID) and fear of hypoglycaemia (HFS).

Results

Of 422 participants (mean ± SD age 37.5 ± 15.0 years; 54% women), 78 (18.5%) reported at least one SH event and 86 (20.5%) had IAH. SH and IAH frequencies were similar at all clinics. In total, 194 SH events were reported, with 10 people experiencing 40% of events. Compared with those without SH, participants with SH had longer diabetes duration, were younger at diabetes onset and more likely to have IAH (p < 0.01). Those with SH had greater fear of hypoglycaemia and diabetes-related distress, poorer general emotional well-being, and lower diabetes-specific positive well-being, (p < 0.01). There were no associations with age, gender, insulin regimen or HbA1c.

Conclusions

This study has identified that SH and IAH in Australian adults with type 1 diabetes exist at similar levels to those reported in US and European research. SH was significantly associated with IAH and fear of hypoglycaemia.Assessment of hypoglycaemia, IAH and psychological well-being as part of a routine diabetes clinic visit was well accepted by attendees and enabled identification of those who may benefit from medical, educational or therapeutic interventions.     

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes

Aims/hypothesis

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention.

Methods

We conducted [¹⁵O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA).

Results

Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2?±?35.5 vs 422.7?±?237.1; neuroglycopenic scores, 34.8?±?88.8 vs 478.9?±?311.1; both p?<?0.002). There were subtle differences (p?<?0.005, k?≥?50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia.

Conclusions/interpretation

Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

     

Spontaneous hypoglycaemia after pancreas transplantation in Type 1 diabetes mellitus

Hypoglycaemia is an important complication of insulin treatment in Type 1 diabetes mellitus (DM). Pancreas transplantation couples glucose sensing and insulin secretion, attaining a distinctive advantage over insulin treatment. We tested whether successful transplantation can avoid hypoglycaemia in Type 1 DM. Combined kidney and pancreas transplanted Type 1 DM who complied with good function criteria (KP-Tx, n = 55), and isolated kidney or liver transplanted non-diabetic subjects on the same immunosuppressive regimen (CON-Tx, n = 14), underwent 1-day metabolic profiles in the first 3 years after transplantation, sampling plasma glucose (PG) and pancreatic hormones every 2 hours. KP-Tx had lower PG than CON-Tx in the night and in the morning and higher insulin concentrations throughout the day. KP-Tx had lower PG nadirs than CON-Tx (4.40 ± 0.05 vs 4.96 ± 0.16 mmol l⁻¹, ANOVA p = 0.001). Nine per cent of KP-Tx had hypoglycaemic values (PG ≤3.0 mmol l⁻¹) in the profiles, both postprandial and postabsorptive, whereas none of CON-Tx did (p < 0.02). In conclusion, after pancreas transplantation, mild hypoglycaemia is frequent, although its clinical impact is limited. Compared to insulin treatment in Type 1 DM, pancreas transplantation improves but cannot eliminate hypoglycaemia. Copyright © 1998 John Wiley & Sons, Ltd.     

Effects of a controlled hypoglycaemia test on QTc in adolescents with Type 1 diabetes

Our objective was to test the ventricular repolarization response to a controlled hypoglycaemia test in Type 1 diabetic adolescents, an age group at risk for ‘dead in bed syndrome’. We measured QTc, blood glucose level, potassium, heart rate, blood pressure and urinary metanephrine levels in 16 Type 1 diabetic adolescents during an insulin clamp mimicking the transition from mild hyperglycaemia to hypoglycaemia. QTc increased in all patients by 146 ± 44 ms (mean ±sd ) ranging from 70 to 230 ms. The longest QTc (630 ms) was recorded in the sibling of a diabetic patient found ‘dead in bed’. Heart rate and urinary metanephrine levels correlated with QTc (r = 0.60 and 0.79, respectively; P = 0.02 and 0.003). QTc in euglycaemia showed no correlation with hypoglycaemia associated QTc prolongation. The prognostic value of the hypoglycaemia test for the risk of recurrent episodes of QTc prolongation should be evaluated in real‐life conditions in large‐scale studies of diabetic adolescents.     

Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week,double-blind,randomized trial

Aims To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. Methods This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. Results Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA_1c) (baseline ≈ 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMΔ) in HbA_1c was −1.4 ± 0.1% and −1.3 ± 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference ≤ 0.4%). The decrease in fasting plasma glucose was similar with acarbose (−1.5 ± 0.2 mmol/l) and vildagliptin (−1.2 ± 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.4 ± 0.1 kg) but decreased in acarbose-treated patients (−1.7 ± 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. Conclusions Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.     

Investigation of quality of life and family burden issues during insulin pump therapy in children with Type 1 diabetes mellitus—a large‐scale multicentre pilot study1

Aims To investigate psychosocial aspects of continuous subcutaneous insulin infusion (CSII) therapy in children with Type 1 diabetes and to identify relevant and sensitive measures. Methods We performed a multi‐centre prospective pre‐/post‐study with children (53 girls, 64 boys, age 10.5 ± 3.7 years, mean ± sd ) with Type 1 diabetes and their main carer from 18 German diabetic centres. Twenty‐five children aged 8–11 years and 63 adolescents aged 12–16 years and their parents, plus 29 parents of children aged 4–7 years completed standardized questionnaires on generic and diabetes‐specific quality of life (QOL), generic parenting stress, mealtime behaviour, fear of hypoglycaemia and family conflict immediately before and 6 months after transition to CSII. Results After transition to CSII, diabetes‐specific QOL of children increased significantly (P < 0.001) in all age groups, with moderate to large effect sizes (children aged 4–7 years: Cohen’s effect sized = 1.3; 8–11 years: d = 0.9, adolescents 12–16 years: d = 0.6). Parents reported reduced frequency (P < 0.01, d = 0.4–0.7) and difficulty (P < 0.01, d = 0.3–0.6) of overall parenting stress and decreased worries about hypoglycaemia (P < 0.01, d = 0.4–0.6). Parents of younger children (4–7 years) reported reduced problems with nutrition management (frequency: P < 0.001, d = 1.1; difficulty: P < 0.05, d = 0.7). Conclusions CSII may have substantial psychosocial benefits. Controlled studies are needed.     

Immigrants from the Middle‐East have a different form of Type 2 diabetes compared with Swedish patients

Aims To compare the clinical characteristics of Type 2 diabetes (T2DM) between immigrants from the Middle‐East and Swedish patients. Methods The study group included 450 consecutive patients with T2DM, 379 Swedish‐born aged 61 ± 12 years and 71 patients originally from the Middle‐East aged 50 ± 11 years from the diabetes clinic of Malmo University Hospital. Results Onset of diabetes had occurred 12 years earlier in the Middle‐East immigrants compared with the Swedish‐born patients (43 ± 10 vs. 55 ± 12 years, P < 0.001). Immigrants had lower fasting serum C‐peptide [0.7 (0.1–2.6) vs. 0.9 (0.1–4.0) nmol/l, P = 0.013], lower homeostasis model assessment (HOMA)‐β[1.7 (0.1–9.1) vs. 2.7 (0.1–59.0), P = 0.010], lower HOMA‐IR [0.4 (0.02–1.19) vs. 0.4 (0.01–2.8), P = 0.005] than the Swedish group. A first‐degree family history of diabetes was reported in 61% of immigrants, compared with 47% of Swedish‐born (P = 0.022). Conclusions Immigrants from the Middle‐East have an earlier onset, stronger family history and more rapid decline of pancreatic B‐cell function than Swedish patients, suggesting that they have a different form of T2DM compared with Swedish patients.     

Diabetes care in hospital—the impact of a dedicated inpatient care team

Aims At any given time, people with diabetes occupy approximately 5–10% of acute hospital beds. In addition, diabetes is associated with a greater length of stay (LOS). This is partially because of increased complexity of the cases but also because of unfamiliarity of dealing with the condition by other specialist teams. Methods In 2002, with increasing pressure on acute hospital beds, a team was established to improve the care of inpatients with diabetes admitted to Derriford Hospital. The team consisted of five diabetes specialist nurses dedicated to inpatient care, supported by a consultant and specialist registrar diabetologist. A link nurse responsible for diabetes was appointed on every ward and each individual with a diagnosis of diabetes was identified on admission. We have compared LOS of all patients with diabetes admitted between January 2002 and December 2006. Results LOS fell from a mean ± se of 8.3 ± 0.18 days in 2002 to 7.7 ± 0.10 days in 2006 (P = 0.002). Significant falls were seen for emergency admissions (9.7 ± 0.23 vs. 9.2 ± 0.20, P < 0.001) but not elective admissions. The data show significant reductions in LOS for medical admissions (9.2 ± 0.24 vs. 8.4 ± 0.20, P < 0.001) but not surgical admissions. Over the same period, LOS for the total hospital population fell by 0.3 days (P < 0.001). Conclusion In conclusion, a team specifically employed to focus on inpatient diabetes care has a significant impact on LOS of this patient group.     

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10–<15, ≥15–<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.     

Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men

Aim The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter‐regulation. Many counter‐regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. Methods Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. Results As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 ± 8 pg/ml) as compared with the first (+54 ± 18 pg/ml) hypoglycaemic clamp (P = 0.046). Conclusion This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter‐regulatory hormones, the hypoglycaemia‐induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined.     

No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed-loop system for 12 weeks: A post hoc secondary analysis of the multicentre,randomized controlled Diabeloop WP7 trial

A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system in controlling the hypoglycaemia induced by physical activity (PA) in real-life conditions. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real-life conditions, the use of DBLG1 avoids PA-induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.     

Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes—the ‘dead in bed’ syndrome revisited

Aims/hypothesis  Sudden nocturnal death in type 1 diabetes (‘dead in bed’ syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. Methods  Twenty-five patients with type 1 diabetes (age 20–50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. Results  There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2–3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 ± 40 vs 415 ± 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). Conclusions/interpretation  This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the ‘dead in bed’ syndrome.     

Frequency,Severity and Symptomatology of Hypoglycaemia: a Comparative Trial of Human and Porcine Insulins in Type 1 Diabetic Patients

A randomized, double-blind, cross-over trial was performed to compare the frequency, severity, and symptomatology of hypoglycaemia during treatment with porcine and human insulins. Forty patients with Type 1 diabetes (20 newly diagnosed and 20 with diabetes of 5–20 years duration) were treated with human and porcine insulins for consecutive 3-month periods, in random order. Episodes of hypoglycaemia were recorded prospectively with self-reporting of the presence and intensity of symptoms using a standardized scoring technique. Serial measurements of glycated haemoglobin and review of home blood glucose tests confirmed that similar glycaemic control was achieved with each insulin species. On comparison of the treatment periods with human and porcine insulins, no differences were demonstrated in the total frequency of symptomatic hypoglycaemia (3.10 vs 3.06 episodes patient^?1 3-months^?1; p = 0.94), the frequency of severe hypoglycaemia (0.1 vs 0.2 episodes patient^?1 3-months^?1; p = 0.44), the occurrence of asymptomatic biochemical hypoglycaemia (0.75 vs 0.68 episodes patient^?1 3-months^?1; p = 0.81), and the capillary blood glucose concentration at the onset of hypoglycaemic symptoms (2.6 ± 0.2 vs 2.4 ± 0.3 mmol I^?1; p = 0.40), with all results being expressed for human vs porcine treatment periods, respectively. The symptoms of hypoglycaemia did not differ during the treatment periods with each insulin species. In conclusion, treatment with human insulin had no effect upon the symptomatic response to hypoglycaemia, did not increase the total frequency of hypoglycaemia, and did not emerge as a significant risk factor for severe hypoglycaemia in these patients.     

A pilot urban church-based programme to reduce risk factors for diabetes among Western Samoans in New Zealand

We have assessed the impact of a 2-year pilot church-base diabetes risk reduction programme on major lifestyle predictors of future Type 2 diabetes mellitus: exercise and weight control in a prospective non-randomized controlled study of a modular lifestyle and diabetes awareness intervention programme using a community development model. The study involved two complete church congregations from an ethnic group at high risk of diabetes (Western Samoans) (intervention church n = 78; control church n = 144). Weight remained stable (0 ± 4.8 kg) in the intervention church but increased by 3.1 ± 9.8 kg in the control church (p = 0.05). In the intervention church, there was an associated reduction in waist circumference (−4 ± 10 cm vs +2 ± 7 cm in control, p < 0.001), an increase in diabetes knowledge (46 ± 26 % vs 4 ± 17 % in control, p < 0.001) and an increase in the proportion exercising regularly (+22 % vs −8 % in control, p < 0.05). Consumption of key fatty foods was also reduced in the intervention church. We conclude that diabetes risk reduction programmes based upon lifestyle change, diabetes awareness, and empowerment of high risk communities can significantly reduce risk factors for future Type 2 diabetes. © 1998 John Wiley & Sons, Ltd.