Differing protocols of managing adult diabetic ketoacidosis outside of the intensive care unit make no difference to the rate of resolution of hyperglycaemia and acidosis.

AIMS: To compare the outcome of people with type 1 diabetes admitted to the general ward with diabetic ketoacidosis (DKA) to two hospitals in Auckland, using different protocols of care. METHODS: North Shore Hospital uses a UK weight-based, ketone centric protocol while Auckland Hospital uses a protocol based on glucose measurements only. All notes of people over 16 years of age admitted to the general wards with DKA to these hospitals in one year were reviewed and their outcome compared. RESULTS: Forty-one admissions in 35 people with DKA at Auckland Hospital were compared to 30 admissions in 26 people with DKA at North Shore Hospital. The degree of ketoacidosis and hyperglycaemia on admission was similar at the two hospitals. The duration of insulin and 10% dextrose infusions was similar but the total number of units of insulin infused and rate of dextrose given per hour were higher at North Shore, with similar rates of hypokalaemia and hypoglycaemic events at each site. The rate of resolution of hyperglycaemia and acidosis did not differ. The length of stay of patients was similar at the two hospitals. CONCLUSIONS: The frequent measurement of bedside ketones did not result in more rapid resolution of DKA compared to relying on glucose measurements alone.

Glucocrinology of Modern Sulfonylureas: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: The primary objective of this document is to develop practice-based expert group opinion on certain important but less discussed endocrine and metabolic effects of modern sulfonylureas (SUs) and their usage in the management of diabetes mellitus (DM). BACKGROUND: Modern SUs may be considered a panacea in DM care with their beneficial extra-pancreatic, pleiotropic, and cardiovascular effects. Safe glycemic control with SUs could be achieved with appropriate patient selection, drug and dosage selection, and patient empowerment. Additionally, sulfonylureas also exhibit certain endocrine and metabolic effects, which could be considered beneficial in the management of DM. In this regard, a group of international clinical experts discussed the less known beneficial aspects of SUs and safe and smart prescription of modern SUs in DM care. RESULTS: The concept of glucocrinology or the relationship of glycemia with the endocrine system was emphasized during the meetings. Clinical experts arrived at a consensus for the usage of modern SUs in the presence of other endocrine dysfunction and the impact of these drugs on endocrine health. The beneficial pleiotropic and cardiovascular effects of modern SUs were also discussed. The key discussion points were considered to develop clinical expert opinions for the use of modern SUs in persons with DM. Clinical expert opinions were developed for indications, pleiotropic benefits, cardiovascular outcomes, adherence, and safe use of modern SUs. CONCLUSIONS: Appropriate clinical judgement coupled with a patient-centered approach is crucial to achieve the best outcome in persons with DM. Owing to their safety, efficacy, extra-pancreatic benefits including effects on endocrine and metabolic aspects, and low cost of therapy, modern SUs could be considered as drugs/agents of choice for the treatment of diabetes. FUNDING: Sanofi India.

Euthymia in Diabetes: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: To develop an evidence-based expert group opinion on various types of euthymia associated with diabetes mellitus (DM) and its management. BACKGROUND: Diabetes mellitus is a metabolic syndrome characterized by diverse biomedical and psychosocial features. Emotional health disturbances may lead to psychological and psychiatric dysfunction and may negatively influence glycemic control. Patients with DM may experience diabetes distress (DD) associated with burden of self-care, interpersonal issues, and emotional worries regarding the ability to cope with the illness. Euthymia or a state of positive mental health and psychological well-being should be considered a key outcome of diabetes care. Therefore, to achieve optimal outcomes, the consideration and measurement of psychological and psychiatric aspects along with glycemic levels are very important. A group of multidisciplinary clinical experts came together in an international meeting held in India to develop a workable concept for euthymia in diabetes care. A multidisciplinary approach was suggested to enhance the clinical outcomes and facilitate patient-centered care. During the meeting emphasis was given to the concept of a euthymia model in diabetes care. This model focuses on enhancement of self-care skills in diabetic patients and preventative health awareness among diabetes care providers. Euthymia also encompasses patient-provider communication to aid enhancement of coping skills. RESULTS: After due discussions and extensive deliberations, the expert group provided several recommendations on implementing the concept of euthymia in DM care. CONCLUSIONS: Introduction of the concept of euthymia in routine clinical practice is important to improve the quality of life and coping skills in patients with DM. A timely clinical assessment of psychological and psychiatric aspects along with patient-reported outcomes of diabetes contributes to overall health and well-being of affected individuals. FUNDING: Sanofi India.

Adherence to medication, glycaemic control and hospital attendance in young adults with type 2 diabetes.

Type 2 diabetes is becoming common among people in their 20s and 30s. Glycaemic control is suboptimal in this group and is associated with poor medication adherence. We studied medication adherence over a 24-month period in all diabetes clinic registrants (n = 266) between the ages of 18 and 39 years. We reviewed their glycaemic control using mean HbA1c over the study period and examined hospital records to determine the number of hospital attendances during this time. We found that less than half the group (47%) had good adherence (>90%) and 21% of the group had very poor adherence (<50%). Mean adherence was slightly poorer in women compared to men (73% vs 76%, P = 0.04). There was a marked inverse relationship between adherence and glycaemic control. Mean HbA1c is 70 mmol/mol among those with good adherence and mean HbA1c is 97 mmol/mol among those with very poor adherence (P < 0.05). Fifty-seven per cent of the study group had at least one hospital attendance during this time. Eighty-eight hospital attendances were due to a medical cause. Study of trend showed more medical admissions among those with very poor adherence (P = 0.03). Mean HbA1c was higher in those who required medical admissions (87 mmol/mol vs 75 mmol/mol) when compared to those with no hospital attendance. Our study shows that poor adherence is common and significantly related to glycaemic control as well as unplanned hospital attendances for medical conditions. Despite limitations, our study provides valuable information on medication adherence and its impact on glycaemic control and morbidity among young people with type 2 diabetes.

Effectiveness of text message based, diabetes self management support programme (SMS4BG): two arm, parallel randomised controlled trial.

OBJECTIVE: To determine the effectiveness of a theoretically based and individually tailored, text message based, diabetes self management support intervention (SMS4BG) in adults with poorly controlled diabetes. DESIGN: Nine month, two arm, parallel randomised controlled trial. SETTING: Primary and secondary healthcare services in New Zealand. PARTICIPANTS: 366 participants aged 16 years and over with poorly controlled type 1 or type 2 diabetes (HbA1c ≥65 mmol/mol or 8%) randomised between June 2015 and November 2016 (n=183 intervention, n=183 control). INTERVENTIONS: The intervention group received a tailored package of text messages for up to nine months in addition to usual care. Text messages provided information, support, motivation, and reminders related to diabetes self management and lifestyle behaviours. The control group received usual care. Messages were delivered by a specifically designed automated content management system. MAIN OUTCOME MEASURES: Primary outcome measure was change in glycaemic control (HbA1c) from baseline to nine months. Secondary outcomes included change in HbA1c at three and six months, and self efficacy, diabetes self care behaviours, diabetes distress, perceptions and beliefs about diabetes, health related quality of life, perceived support for diabetes management, and intervention engagement and satisfaction at nine months. Regression models adjusted for baseline outcome, health district category, diabetes type, and ethnicity. RESULTS: The reduction in HbA1c at nine months was significantly greater in the intervention group (mean -8.85 mmol/mol (standard deviation 14.84)) than in the control group (-3.96 mmol/mol (17.02); adjusted mean difference -4.23 (95% confidence interval -7.30 to -1.15), P=0.007). Of 21 secondary outcomes, only four showed statistically significant improvements in favour of the intervention group at nine months. Significant improvements were seen for foot care behaviour (adjusted mean difference 0.85 (95% confidence interval 0.40 to 1.29), P<0.001), overall diabetes support (0.26 (0.03 to 0.50), P=0.03), health status on the EQ-5D visual analogue scale (4.38 (0.44 to 8.33), P=0.03), and perceptions of illness identity (-0.54 (-1.04 to -0.03), P=0.04). High levels of satisfaction with SMS4BG were found, with 161 (95%) of 169 participants reporting it to be useful, and 164 (97%) willing to recommend the programme to other people with diabetes. CONCLUSION: A tailored, text message based, self management support programme resulted in modest improvements in glycaemic control in adults with poorly controlled diabetes. Although the clinical significance of these results is unclear, the findings support further investigation into the use of SMS4BG and other text message based support for this patient population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001232628.

Type 2 diabetes in young adults in Central Auckland: demography and complications.

BACKGROUND: Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications. AIMS: To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration. METHODS: In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications. RESULTS: Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand-born Pasifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty-four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4-5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001). CONCLUSIONS: New migrants, New Zealand-born Pasifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.

23 years of managing diabetic ketoacidosis at Auckland Hospital

AIMS: To examine the length of stay and need for intensive care of people admitted with diabetic ketoacidosis (DKA) to a single centre between 1988 and 2011. METHODS: Patients aged ≥15 years admitted for the first time with DKA (plasma glucose ≥ 10mmol/L and a bicarbonate concentration ≤15mmol/L and a pH <7.35, and raised plasma or urine ketones or anion gap) to Auckland City Hospital from 1988-2011 were identified retrospectively. The patients were divided into four cohorts (1988-1996; 1997-2001; 2002-2006; 2007-2011). Over this time period there was no significant change to the insulin infusion protocol. RESULTS: There were 576 admissions with DKA in 388 people over the 23 years. The mean age of the patients and glucose concentration at presentation to hospital fell significantly over time. The admission pH and bicarbonate concentration was higher in more recent cohorts. The length of stay and need for intensive care admission fell significantly over time, but the number of patients subsequently readmitted with DKA remained high. In-hospital mortality remained low. CONCLUSIONS: DKA remains an important reason for admission to this hospital, but the severity of DKA at presentation has reduced over time. The need for intensive care admission and length of stay has fallen dramatically.

The Use of Mobile Health to Deliver Self-Management Support to Young People With Type 1 Diabetes: A Cross-Sectional Survey.

BACKGROUND: Young people living with type 1 diabetes face not only the challenges typical of adolescence, but also the challenges of daily management of their health and evolving understanding of the impact of their diagnosis on their future. Adolescence is a critical time for diabetes self-management, with a typical decline in glycemic control increasing risk for microvascular diabetes complications. To improve glycemic control, there is a need for evidence-based self-management support interventions that address the issues pertinent to this population, utilizing platforms that engage them. Increasingly, mobile health (mHealth) interventions are being developed and evaluated for this purpose with some evidence supporting improved glycemic control. A necessary step to enhance effectiveness of such approaches is to understand young people's preferences for this mode of delivery. OBJECTIVE: A cross-sectional survey was conducted to investigate the current and perceived roles of mHealth in supporting young people to manage their diabetes. METHODS: Young adults (16-24 years) with type 1 diabetes in Auckland, New Zealand, were invited to take part in a survey via letter from their diabetes specialist. RESULTS: A total of 115 young adults completed the survey (mean age 19.5 years; male 52/115, 45%; European 89/115, 77%), with all reporting they owned a mobile phone and 96% (110/115) of those were smartphones. However, smartphone apps for diabetes management had been used by only 33% (38/115) of respondents. The most commonly reported reason for not using apps was a lack of awareness that they existed. Although the majority felt they managed their diabetes well, 63% (72/115) reported wanting to learn more about diabetes and how to manage it. A total of 64% (74/115) respondents reported that they would be interested in receiving diabetes self-management support via text message (short message service, SMS). CONCLUSIONS: Current engagement with mHealth in this population appears low, although the findings from this study provide support for the use of mHealth in this group because of the ubiquity and convenience of mobile devices. mHealth has potential to provide information and support to this population, utilizing mediums commonplace for this group and with greater reach than traditional methods.

Text message-based diabetes self-management support (SMS4BG): study protocol for a randomised controlled trial.

BACKGROUND: Addressing the increasing prevalence, and associated disease burden, of diabetes is a priority of health services internationally. Interventions to support patients to effectively self-manage their condition have the potential to reduce the risk of costly and debilitating complications. The utilisation of mobile phones to deliver self-management support allows for patient-centred care at the frequency and intensity that patients desire from outside the clinic environment. Self-Management Support for Blood Glucose (SMS4BG) is a novel text message-based intervention for supporting people with diabetes to improve self-management behaviours and achieve better glycaemic control and is tailored to individual patient preferences, demographics, clinical characteristics, and culture. This study aims to assess whether SMS4BG can improve glycaemic control in adults with poorly controlled diabetes. This paper outlines the rationale and methods of the trial. METHODS/DESIGN: A two-arm, parallel, randomised controlled trial will be conducted across New Zealand health districts. One thousand participants will be randomised at a 1:1 ratio to receive SMS4BG, a theoretically based and individually tailored automated text message-based diabetes self-management support programme (intervention) in addition to usual care, or usual care alone (control). The primary outcome is change in glycaemic control (HbA1c) at 9 months. Secondary outcomes include glycaemic control at 3 and 6 months, self-efficacy, self-care behaviours, diabetes distress, health-related quality of life, perceived social support, and illness perceptions. Cost information and healthcare utilisation will also be collected as well as intervention satisfaction and interaction. DISCUSSION: This study will provide information on the effectiveness of a text message-based self-management support tool for people with diabetes. If found to be effective it has the potential to provide individualised support to people with diabetes across New Zealand (and internationally), thus extending care outside the clinic environment. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12614001232628 .

Practical Guidance on the Use of Premix Insulin Analogs in Initiating, Intensifying, or Switching Insulin Regimens in Type 2 Diabetes.

INTRODUCTION: Premix insulin analogs are a well-established treatment for type 2 diabetes (T2D). However, there is a lack of simple, clear guidance on some aspects of their use. These include choosing a regimen for insulin initiation, recognizing when patients need intensification of therapy, and switching from basal-bolus to a premix insulin analog when appropriate. METHODS: An independent expert panel formulated recommendations on the use in T2D of the premix insulin analog formulations widely available in Australasia, based on the available evidence and their own experience. RESULTS: Results from trials in both initiation and intensification of insulin show that no single insulin or regimen is best on all endpoints, and that improved glycemic control can be expected regardless of which regimen is used. Thus, individual patient factors and preferences become more important. Guidance is presented to help the clinician choose between a premix insulin analog or basal analog for insulin initiation, and to intensify insulin therapy using premix insulin analogs. Recommendations are made on dosing, titration, the concomitant use of non-insulin glucose-lowering drugs, and other practical issues, and on the special case of switching from basal-bolus to premix insulin analog therapy. CONCLUSION: This guidance is intended to help both general and specialist practitioners make informed choices and provide optimal care for patients with T2D. It emphasizes the importance of taking into account individual patient factors and preferences so that the choice of insulin regimen is individualized to the patient in the same way that glycemic targets are now individualized. FUNDING: Novo Nordisk Region IO A/S.

Starting insulin in type 2 diabetes: real-world outcomes after the first 12 months of insulin therapy in a new zealand cohort.

AIMS: Currently, there is no consensus on which form of insulin to use when initiating insulin in type 2 diabetes (T2D). Our aim was to compare glycated hemoglobin (HbA1C) reduction, weight change and severe hypoglycemia rates during the first year after initiation of intermediate-acting insulin isophane, insulin glargine and pre-mixed insulin in patients with T2D. METHODS: Electronic clinical records of patients with T2D, starting insulin at a tertiary referral center in Auckland, New Zealand, from January 1 to December 31, 2012, were retrospectively evaluated. Primary outcomes were HbA1C reduction at 12 months and number of hospital admissions for hypoglycemia. RESULTS: Of 339 eligible patients, 273 (80.5%) started on intermediate insulin, 24 started on insulin glargine and 42 started on pre-mixed insulin. The mean HbA1C at insulin initiation was 89-95 mmol/mol, but had decreased at 12 months by 26.6 mmol/mol with insulin glargine, 23.4 mmol/mol with pre-mixed insulin and 16.6 mmol/mol with insulin isophane (p < 0.05 vs. baseline for all groups). Patients on insulin glargine were more likely to achieve the HbA1C target of <55 mmol/mol compared with patients on insulin isophane (16.7% vs. 4.8%; p = 0.04). Persistence rates were higher in patients initiated on pre-mixed insulin vs. insulin isophane (90.5% vs. 69.6%; p = 0.01). After controlling for confounding variables, glargine was more likely to achieve an HbA1C target of <55 (p = 0.05). CONCLUSIONS: All insulin types caused a significant reduction in HbA1C, but very few met HbA1C targets. Insulin isophane was the most common type of insulin prescribed at initiation, with comparable outcomes to other types of insulin. More observational studies are needed to explore the possible impact of using other insulin types at initiation.

Visfatin is regulated by rosiglitazone in type 2 diabetes mellitus and influenced by NFκB and JNK in human abdominal subcutaneous adipocytes.

Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM. Firstly, we examined the effects of diabetic status on circulating visfatin levels, and several other adipocytokines, demonstrating that diabetic status increased visfatin*, TNF-α*** and IL-6*** compared with non-diabetic subjects (*p<0.05, **p<0.01, ***p<0.001, respectively). We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naïve T2DM subjects, on circulating visfatin levels. Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation. Further studies addressed the intracellular mechanisms by which visfatin may be regulated, and may exert pro-inflammatory effects, in human abdominal subcutaneous (Abd Sc) adipocytes. Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKKß** and p-JNK1/2*. Furthermore, inhibition of JNK protein exacted a significant reduction in visfatin expression (**p<0.01), whilst NF-κB blockade increased visfatin (*p<0.05), thus identifying JNK as the more influential factor in visfatin regulation. Additional in vitro analysis on adipokines regulating visfatin showed that only Abd Sc adipocytes treated with recombinant human (rh)IL-6 increased visfatin protein (*p<0.05), whilst rh visfatin treatment, itself, had no influence on TNF-α, IL-6 or resistin secretion from Sc adipocytes. These data highlight visfatin's regulation by insulin and RSG, potentially acting through NF-κB and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation. Taken together, these findings suggest that visfatin may represent a pro-inflammatory cytokine that is influenced by insulin/insulin sensitivity via the NF-κB and JNK pathways.

The biological relevance and measurement of plasma markers of oxidative stress in diabetes and cardiovascular disease.

Oxidative stress is associated with many chronic diseases. In this review, we look at the role that oxidative stress may play in diabetes and related cardiovascular disease (CVD) and how oxidative damage may be measured in the plasma. Increased production of reactive oxygen species (ROS) has been implicated in the initiation and progression of both of these conditions and it may be that oxidative stress accounts for the unexplained increase in cardiovascular risk observed in diabetes. Plasma measurements are difficult because of the highly reactive nature of these molecules. Several studies have focused on measuring the total antioxidant buffering capacity of plasma or alternatively specific measures of free radical-mediated damage such as F(2)-isoprostane or oxidised-LDL (Ox-LDL). Perhaps, in the future, the discovery of an 'easy to measure marker' of oxidative stress might be incorporated into risk prediction in diabetes and cardiovascular disease.