Prevention and Management of Severe Hypoglycemia and Hypoglycemia Unawareness: Incorporating Sensor Technology

Purpose of Review

In addition to assisting in achieving improved glucose control, continuous glucose monitoring (CGM) sensor technology may also aid in detection and prevention of hypoglycemia. In this paper, we report on the current scientific evidence on the effectiveness of this technology in the prevention of severe hypoglycemia and hypoglycemia unawareness.

Recent Findings

Recent studies have found that the integration of CGM with continuous subcutaneous insulin infusion (CSII) therapy, a system known as sensor-augmented pump (SAP) therapy, very significantly reduces the occurrence of these conditions by providing real-time glucose readings/trends and automatically suspending insulin infusion when glucose is low (LGS) or, even, before glucose is low but is predicted to soon be low (PLGS). Initial data indicate that even for patients with type 1 diabetes treated with multiple daily injections, real-time CGM alone has been found to reduce both severe hypoglycemia and hypoglycemia unawareness. Closed loop systems (artificial pancreas) comprised of CGM and CSII without patient intervention to adjust basal insulin, which automatically reduce, increase, and suspend insulin delivery, represent a potential new option that is moving toward becoming a reality in the near future.

Summary

Sensor technology promises to continue to improve patients’ lives not only by attaining glycemic control but also by reducing hypoglycemia, a goal best achieved in conjunction with structured individualized patient education.

     

A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation

Aims

Insulin resistance underlies the etiology of both type 2 diabetes and gestational diabetes. In pregnancy, insulin resistance is also associated with an unfavorable metabolic programming of the fetus, potentially contributing to a higher risk of obesity and type 2 diabetes in the offspring. To assess insulin sensitivity, several methods based on glucose and insulin levels during a 75-g oral glucose tolerance test (OGTT) exist. It is unclear how they perform during pregnancy, where physiologically altered metabolism could introduce a bias.

Methods

In a cohort comprising 476 non-diabetic subjects undergoing OGTT and hyperinsulinemic-euglycemic clamp (HEC), we used cross-validation to develop an insulin sensitivity index also based on non-esterified fatty acids (NEFA) that could be more robust during pregnancy (NEFA-index). We tested commonly used OGTT-based indexes and the NEFA-index in a different cohort of 42 women during pregnancy and 1 year after delivery.

Results

The Matsuda and OGIS index failed to detect lower insulin sensitivity during pregnancy as compared to the follow-up OGTT 1 year after delivery (p > 0.09). The new NEFA-index incorporating BMI, plasma insulin and NEFA, but not glucose, clearly indicated lower insulin sensitivity during pregnancy (p < 0.0001). In the non-pregnant cohort, this NEFA-index correlated well with the gold-standard HEC-based insulin sensitivity index, and outperformed other tested indexes for the prediction of HEC-measured insulin resistance.

Conclusions

This insulin/NEFA-based approach is feasible, robust, and could be consistently used to estimate insulin sensitivity also during pregnancy.

     

Designing the Glucose Telemetry for Hospital Management: From Bedside to the Nursing Station

Purpose of the Review

Hospitalized patients with diabetes are monitored with point-of-care glucose testing. Continuous glucose monitoring (CGM) devices represent an alternative way to monitor glucose values; however, the in-hospital CGM use is still considered experimental. Most inpatient studies used “blinded” CGM properties and only few used the real-time/unblinded CGM features. One major limitation of the CGM devices is that they need to be placed at the patients’ bedside, limiting any therapeutic interventions. In this article, we review the real-time/unblinded CGM use and share our thoughts about the development of future inpatient CGM systems.

Recent Findings

We recently reported that glucose values can be wirelessly transmitted to the nursing station, providing remote continuous glucose monitoring.

Summary

Future inpatient CGM devices may be utilized for patients at risk for hypoglycemia similarly to the way that we use cardiac telemetry to monitor hospitalized patients who are at increased risk for cardiac arrhythmias.

     

Kardiovaskuläre Effekte der Insulintherapie

Background

The importance of a near normal blood glucose adjustment and insulin therapy for prevention of subsequent microangiopathic diseases is undisputed.

Type 1 diabetes

The important role of intensive insulin therapy for prevention of cardiovascular events in type 1 diabetes has been clearly confirmed by the diabetes control and complications trial (DCCT) of the epidemiology of diabetes interventions and complications (EDIC) research group: in the long term, intensive insulin therapy reduces the risk of non-fatal myocardial infarction, stroke and death from cardiovascular causes by 57?%.

Type 2 diabetes

For patients with type 2 diabetes a cardiovascular benefit of early insulin therapy with near normal blood glucose adjustment was confirmed by the United Kingdom prospective diabetes study (UKPDS) but only becomes apparent in the follow-up period. In insulin therapy of long-standing diabetes mellitus and/or pre-existing cardiovascular diseases, priority is given to avoidance of hypoglycemia in order to prevent acute cardiovascular events. For patients with heart insufficiency the indications are that high insulin dosages should be avoided where possible and the benefit of a near normal blood glucose adjustment has also not been proven.

     

Biopsychosocial Factors Associated With Satisfaction and Sustained Use of Artificial Pancreas Technology and Its Components: a Call to the Technology Field

Purpose of Review

Summarize biopsychosocial factors associated with using continuous glucose monitors (CGMs), insulin pumps, and artificial pancreas (AP) systems and provide a “call to the field” about their importance to technology uptake and maintained use.

Recent Findings

Insulin pumps and CGMs are becoming standard of care for individuals with type 1 diabetes (T1D). AP systems combining a CGM, insulin pump, and automated dosing algorithm are available for commercial use. Despite improved glycemic control with AP system use, numerous barriers exist which may limit their benefit. Studies on components of AP systems (pumps, CGMs) are limited and demonstrate mixed results of their impact on fear of hypoglycemia, adherence, quality of life, depression and anxiety, and diabetes distress. Studies examining biopsychological factors associated specifically with sustained use of AP systems are also sparse.

Summary

Biological, psychological and social impacts of AP systems have been understudied and the information they provide has not been capitalized upon.

     

Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery

Aims/hypothesis

A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls.

Methods

Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n?=?76 per group, matched for age and date of delivery).

Results

Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants.

Conclusions/interpretation

Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

     

Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT)

Purpose of Review

The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth.

Recent Findings

Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility.

Summary

Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.

     

Transplantation of Macroencapsulated Insulin-Producing Cells

Purpose of Review

There is considerable interest in using macroencapsulation devices as a delivery strategy for transplanting insulin-producing cells. This review aims to summarize recent advances, to highlight remaining challenges, and to provide recommendations for the field.

Recent Findings

A variety of new device designs have been reported to improve biocompatibility and to provide protection for islet/beta cells from immune destruction while allowing continuous secretion of insulin. Some of these new approaches are in clinical trials, but more research is needed to determine how sufficient beta-cell mass can be transplanted in a clinically applicable device size, and that insulin is secreted with kinetics that will safely provide adequate controls of glucose levels.

Summary

Macroencapsulation is a potential solution to transplant beta cells without immunosuppression in diabetes patients, but new strategies must be developed to show that this approach is feasible.

     

Translating HbA<Subscript>1c</Subscript> measurements into estimated average glucose values in pregnant women with diabetes

Aims/hypothesis

This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA_1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA_1c measurements are applicable to pregnant women with diabetes.

Methods

CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5–7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA_1c measure. In total, 688 average glucose–HbA_1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA_1c.

Results

There was a strong association between HbA_1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA_1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA_1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4–7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA_1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week.

Conclusions/interpretation

The HbA_1c–average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.

     

Hepatogener Diabetes

Background

Disturbances of glucose metabolism are common in chronic liver disease and about 30–40?% of patients with liver cirrhosis develop type 2 diabetes. The diabetes may be a direct consequence of the hepatic disease due to excessive insulin resistance or may be caused by classical type 2 diabetes.

Blood glucose determination

Patients with chronic liver disease frequently have a normal fasting glucose despite manifest type 2 diabetes with postprandial excessive increases in glucose. Therefore, oral glucose tolerance tests should be performed after diagnosis of hepatic cirrhosis.

Prognosis

Diabetes mellitus is associated with increased mortality and an increased risk of complications of liver cirrhosis including premature death, hepatocellular carcinoma, hepatic encephalopathy, and spontaneous bacterial peritonitis. Therapy of diabetes should include metformin and α?glucosidase inhibitors which can reduce the risk of these complications. Therefore, the diagnosis of diabetes has important consequences in chronic liver disease.

     

Clinical Management of Women with Monogenic Diabetes During Pregnancy

Purpose of Review

Monogenic diabetes accounts for 1–2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for K_ATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management. Here, we discuss the key issues in pregnancy affected by monogenic diabetes.

Recent Findings

General recommendations for pregnancy affected by GCK-MODY determine need for maternal insulin treatment based on fetal mutation status. However, a recent study suggests macrosomia and miscarriage rates may be increased with this strategy. Recent demonstration of transplacental transfer of sulfonylureas also raises questions as to when insulin should be initiated in sulfonylurea-responsive forms of monogenic diabetes.

Summary

Pregnancy represents a challenge in management of monogenic diabetes, where factors of maternal glycemic control, fetal mutation status, and transplacental transfer of medication must all be taken into consideration. Guidelines for pregnancy affected by monogenic diabetes will benefit from large, prospective studies to better define the need for and timing of initiation of insulin treatment.

     

Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An Analysis of the Look AHEAD Randomized Trial

Background

The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood.

Objective

We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial.

Design

Retrospective analysis of a randomized clinical trial.

Participants

Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline.

Main Measures

We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors.

Key Results

A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P?=?0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P?<?0.001 for trend); chronic kidney disease and cardiovascular disease were independently associated with insulin initiation. There was a lower risk of insulin initiation in black (aHR 0.77, P?=?0.008) and Hispanic participants (aHR 0.66, P?<?0.001) relative to white participants. Socioeconomic factors were not associated with insulin initiation.

Conclusions

Patient age, race/ethnicity, and diabetes complications may influence insulin initiation in type 2 diabetes, independent of glycemic control. Future work is needed to understand the drivers of racial differences in antihyperglycemic treatment, and to identify patients who benefit most from insulin.

     

Adipose-derived lipocalin 14 alleviates hyperglycaemia by suppressing both adipocyte glycerol efflux and hepatic gluconeogenesis in mice

Aims/hypothesis

Growing evidence supports that dysregulation of adipose tissue-derived factors contributes to the pathogenesis of diabetes and its complications. Since our global gene profiling analysis has identified lipocalin-14 (LCN14)—a secretory protein with lipid-binding properties—as a potential adipokine highly expressed in white adipose tissue (WAT), this study aims to explore the metabolic roles of LCN14 in obese mice, and to investigate the functional mechanisms involved.

Methods

Immunoassays and western blotting were performed to determine the circulating level and tissue distribution of LCN14, respectively. Recombinant adeno-associated virus (rAAV)-mediated gene delivery was used to overexpress LCN14 in diet-induced obese (DIO) mice and the effects on glucose and lipid metabolism were examined.

Results

LCN14 is expressed predominantly in WAT. Both circulating levels of LCN14 and its expression in adipose tissues are repressed in DIO and genetically inherited diabetic (db/db) mice. Overexpression of LCN14 by rAAV-mediated gene delivery in DIO mice significantly increased insulin sensitivity in major metabolic tissues and ameliorated hyperglycaemia by inhibiting hepatic gluconeogenesis. The reduced hepatic glucose production is attributed to the suppressive effects of LCN14 on the expression of gluconeogenic genes and on glycerol efflux in adipocytes, possibly by reducing the expression of aquaporin-7.

Conclusions/interpretation

Reduced LCN14 expression is involved in the pathogenesis of obesity-related metabolic dysregulation. LCN14 exerts its beneficial effects on glucose homeostasis and insulin sensitivity via its actions in both adipocytes and hepatocytes.

     

Gut Microbiome in Obesity,Metabolic Syndrome,and Diabetes

Purpose of Review

Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

Recent findings

Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.

Summary

While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.

     

Maternal Non-glycemic Contributors to Fetal Growth in Obesity and Gestational Diabetes: Spotlight on Lipids

Purpose of Review

Excess fetal growth is increasingly recognized as a risk factor for childhood obesity, and mounting evidence supports that maternal glucose is not the only driver. This review focuses on the role of clinically applicable maternal non-glycemic contributors to excess fetal growth, particularly lipids, in addition to amino acids (AA), insulin resistance, inflammation, maternal nutrition, and gestational weight gain (GWG) in obesity and gestational diabetes mellitus (GDM).

Recent Findings

Lipids, specifically triglycerides and free fatty acids, appear to be strong contributors to excess fetal fat accretion and adiposity at birth, particularly in obese pregnancies, which account for the largest number of large-for-gestational-age infants. Maternal pre-pregnancy body mass index (BMI), GWG, insulin resistance, inflammation, and glucose, lipid, and AA concentrations have both independent and interacting effects on fetal growth, operating both early and late in pregnancy. All are sensitive to maternal nutrition.

Summary

Early vs. later gestational exposure to excess maternal fuels in fasting and postprandial conditions may differentially impact fetoplacental outcomes. Compelling evidence suggests that targeting interventions early in pregnancy beyond glucose may be critical to improve fetal growth patterns.

     

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

BACKGROUND

Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited.

OBJECTIVE

To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin.

DESIGN

This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases.

PARTICIPANTS

Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011.

MAIN MEASURES

The association between insulin versus sulfonylurea?+?insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min.

KEY FINDINGS

There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea?+?insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings.

CONCLUSIONS

Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.

     

Artificial Pancreas or Novel Beta-Cell Replacement Therapies: a Race for Optimal Glycemic Control?

Purpose of Review

New treatment strategies are needed for patients with type 1 diabetes (T1D). Closed loop insulin delivery and beta-cell replacement therapy are promising new strategies. This review aims to give an insight in the most relevant literature on this topic and to compare the two radically different treatment modalities.

Recent Findings

Multiple clinical studies have been performed with closed loop insulin delivery devices and have shown an improvement in overall glycemic control and time spent in hypoglycemia. Beta-cell transplantation has been shown to normalize or greatly improve glycemic control in T1D, but the donor organ shortage and the necessity to use immunosuppressive agents are major drawbacks. Donor organ shortage may be solved by the utilization of stem cell-derived beta cells, which has shown great promise in animal models and are now tested in clinical studies. Immunosuppression may be avoided by encapsulation.

Summary

Closed loop insulin delivery devices are promising treatment strategies and are likely to be used in clinical practice in the short term. But this approach will always suffer from delays in glucose measurement and insulin action preventing it from normalizing glycemic control. In the long term, stem cell-derived beta cell transplantation may be able to achieve this, but wide implementation in clinical practice is still far away.

     

Closed-loop glucose control in young people with type 1 diabetes during and after unannounced physical activity: a randomised controlled crossover trial

Aims/hypothesis

Hypoglycaemia during and after exercise remains a challenge. The present study evaluated the safety and efficacy of closed-loop insulin delivery during unannounced (to the closed-loop algorithm) afternoon physical activity and during the following night in young people with type 1 diabetes.

Methods

A randomised, two-arm, open-label, in-hospital, crossover clinical trial was performed at a single site in Slovenia. The order was randomly determined using an automated web-based programme with randomly permuted blocks of four. Allocation assignment was not masked. Children and adolescents with type 1 diabetes who were experienced insulin pump users were eligible for the trial. During four separate in-hospital visits, the participants performed two unannounced exercise protocols: moderate intensity (55% of \( \overset{\cdot }{V}{\mathrm{O}}_{2\max } \)) and moderate intensity with integrated high-intensity sprints (55/80% of \( \overset{\cdot }{V}{\mathrm{O}}_{2\max } \)), using the same study device either for closed-loop or open-loop insulin delivery. We investigated glycaemic control during the exercise period and the following night. The closed-loop insulin delivery was applied from 15:00 h on the day of the exercise to 13:00 h on the following day.

Results

Between 20 January and 16 June 2016, 20 eligible participants (9 female, mean age 14.2 ± 2.0 years, HbA_1c 7.7 ± 0.6% [60.0 ± 6.6 mmol/mol]) were included in the trial and performed all trial-mandated activities. The median proportion of time spent in hypoglycaemia below 3.3 mmol/l was 0.00% for both treatment modalities (p = 0.7910). Use of the closed-loop insulin delivery system increased the proportion of time spent within the target glucose range of 3.9–10 mmol/l when compared with open-loop delivery: 84.1% (interquartile range 70.0–85.5) vs 68.7% (59.0–77.7), respectively (p = 0.0057), over the entire study period. This was achieved with significantly less insulin delivered via the closed-loop (p = 0.0123).

Conclusions/interpretation

Closed-loop insulin delivery was safe both during and after unannounced exercise protocols in the in-hospital environment, maintaining glucose values mostly within the target range without an increased risk of hypoglycaemia.

Trial registration

Clinicaltrials.gov NCT02657083

Funding

University Medical Centre Ljubljana, Slovenian National Research Agency, and ISPAD Research Fellowship

     

Digitalisierung in der alltäglichen Praxis

Background

The digitization of medicine in clinical practice as well as the digitization and the use of diabetes technologies has been an exciting and sometimes difficult process for a variety of reasons. Although establishing technologies in medical practice is helpful, it also means work associated with convincing others regarding this, whereby less work is needed to convince our patients.

Aim of the article

Using the example of our diabetological endocrinological outpatient clinic, we want to show which hurdles had to be overcome and which advantages we see from a digital orientation.

Conclusion

By using diabetes technologies, we see clear benefits of more individualized therapy. So-called “talking medicine” has come more into the foreground and the data gained from this technology support this claim of individualized medicine.

     

The effect of interleukin-22 treatment on autoimmune diabetes in the NOD mouse

Aims/hypothesis

The aim of this study was to determine whether therapy with the cytokine IL-22 could be used to prevent the development of, or treat, autoimmune diabetes in the NOD mouse.

Methods

Six-week-old NOD mice were administered bi-weekly either recombinant mouse IL-22 (200 ng/g) or PBS (vehicle control) intraperitoneally until overt diabetes was diagnosed as two consecutive measurements of non-fasting blood glucose ≥ 11 mmol/l. At this time, NOD mice in the control arm were treated with LinBit insulin pellets and randomised to bi-weekly therapeutic injections of either PBS or IL-22 (200 ng/g) and followed until overt diabetes was diagnosed, as defined above.

Results

IL-22 therapy did not delay the onset of diabetes in comparison with the vehicle-treated mice. We did not observe an improvement in islet area, glycaemic control, beta cell residual function, endoplasmic reticulum stress, insulitis or macrophage and neutrophil infiltration as determined by non-fasting blood glucose, C-peptide and histological scoring. Therapeutic administration of IL-22 did not reduce circulating lipopolysaccharide, a marker of impaired gut mucosal integrity.

Conclusions/interpretation

Our study suggests that, at this dosing regimen introduced either prior to overt diabetes or at diagnosis of diabetes, recombinant mouse IL-22 therapy cannot prevent autoimmune diabetes, or prolong the honeymoon period in the NOD mouse.