Essay: Understanding Diabetes Mellitus: Symptoms, Types, and Complications

INTRODUCTION:
Diabetes mellitus is commonly known as diabetes, it is a group of metabolic diseases in which a high blood sugar levels over a prolonged period.1 High blood sugar levels include the symptoms like increased thirst, increased hunger and frequent urination. Untreated diabetes can cause many complications. There are two type of complications i.e., acute complication and serious long term complications.2 Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long term complications include cardiovascular disease, chronic kidney failure foot ulcers, stroke and damage to the eyes.
Diabetes is mainly due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.3 Mainly 3 types of diabetes mellitus
 Type 1 DM
 Type2 DM
 Gestational diabetes mellitus (GDM)
The pancreas’s failure to produce enough insulin it is known as type1 DM or otherwise known as “insulin dependent diabetes mellitus “(IDDM) or” juvenile diabetes”. The cause is unknown and it is not preventable with current knowledge.
Type 2 DM starts with insulin resistance, this is a condition in which the improper responds to the insulin produced . As the disease progresses a lack of insulin may also develop. This is also known as “insulin-independent diabetes mellitus” (NIDDM) or “adult –onset diabetes”. The primary cause is excessive body weight and not enough exercise.
Gestational diabetes occurs in pregnant women without a previous history of diabetes develops a high-blood sugar.4
TYPE 1 DM
This is characterized lack of insulin producing beta cells of the islets of Langerhans in the pancreas, which will lead to insulin deficiency. Type 1 diabetes mellitus can be further classified as immune-mediated or idiopathic.5 The most of type 1 diabetes is of the immune mediated- nature, in which a T-cell -mediated autoimmune attack, leads to the loss of beta cells thus insulin. Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision change and fatigue. This symptom may occur suddenly. It causes approximately 10% of diabetes mellitus cases in North America and Europe.
Right now the treatment of the disease is insulin injections. A basal bolus regimen, where a specific dose of insulin is administered after every meal to control sugar levels throughout the day is usually a preferred option by parents
According to world health organization:
The number of people with diabetes has risen from 108 million in 2014
 The global prevalence of diabetes*among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014
 Diabetes prevalence has been rising more rapidly in middle – and low – income countries Diabetes is a major cause of blindness kidney failure, heart attacks, stroke and lower limb amputation
 In 2012, an estimated 1.5 million deaths were directly caused by diabetes and another 2.2 million deaths were attributable to high blood glucose.
 Almost half of all deaths attributable to high blood glucose occur before the age of 70 years. WHO projects that diabetes will be the 7th leading cause of death in 2030
 Healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use are ways to prevent or delay the onset of type 2 diabetes
 Diabetes can be treated and its consequences avoided or delayed with diet, physical activity, medication and regular screening and treatment for complications.6
Type 1diabetes mellitus (T1DM) subjects and most of the type2 diabetes mellitus (T2DM)subjects require insulin to sustain life .Syringes and pens are the most popular insulin delivery device. Insulin pumps are more commonly used because of its unique ability to continuously infuse insulin, its closely mimicking that of the physiological secretion from a normal pancreas.
Insulin pump otherwise known as continuous subcutaneous insulin infusion (CSII). It is a mobile sized device that can be connected to the body through an infusion set so as to deliver insulin continuously. it consist of disposable reservoir for insulin and a disposable infusion set, including a cannula for subcutaneous insertion and a tubing system that connects the insulin reservoir to the cannula. Pump therapy is an alternative delivery mechanism for insulin administration and is superior to ordinary syringes and insulin pen.
EVOLUTION OF PUMP THERAPY
 The first insulin pump was introduced in the early 1960s by a Los Angeles doctor by the name of Arnold kadish . The first model was so big that it had to be worn like a back pack.
 In the beginning of 1990s more user friendly models appeared with features like bolus calculators and compatibility with personal computers so that users could have greater control of their insulin intake and monitor their blood glucose level more efficiently.
 In 2006 Medtronic, Minimed (Northridge,CA) , historically recognized as pioneers in insulin pump therapy , introduced real time insulin pumps where the glucose sensor and the pump were combined .
 The introduction of real-time insulin pump was a major breakthrough toward “closing the loop” of insulin delivery, very near to the dream of inventing fully automatic device . At present in India, apart from medtronic (Northridge,CA) devices , Roche (Basel , Switzerland ) pumps are also available.
The continuous subcutaneous insulin infusion pump is a mobile sized device which can be connected to the body via an infusion set so as to deliver insulin continuously. It consist of a disposable infusion set including cannula for subcutaneous insertion , disposable reservoir for insulin and a tubing system which connect insulin reservoir to the cannula . Pump therapy itself is not a new therapy for diabetes mellitus. It is another way of delivering mechanism for administration of insulin. Pump therapy is found to be superior to the ordinary syringes and insulin pens. Subcutaneous insulin administration via a properly programmed insulin pump, insulin delivery is expected to mimic release pattern of insulin, by a normal healthy pancreas better than other insulin delivery modalities. Willingness of the patient is absolutely essential before going on a pump.
A quarter of centaury after its introduction the use of insulin pump in world- wide is increasing. . Review showed that , in most patients , mean blood glucose concentration HbA1C percentage are either slightly lower or similar on insulin pump versus MDI . Hypoglycemic episodes are less frequent than the MDI. Ketoacidosis occurs at the same rate. Reduction in HbA1c value in type 1 diabetes mellitus can be obtained by continuous glucose monitoring.
Diabetic control and complication trail highlighted the importance of achieving the importance of tight metabolic control and improving the long- term health outcomes in type 1 diabetes mellitus patient. The release of diabetic control and complication trial renewed the interest and role of continuous subcutaneous insulin infusion via individual insulin pump improving diabetes treatment.
Guidelines on Insulin pump
According to National Institute for Health and Clinical excellence guidelines, insulin pump should be initiated only in a center with sufficient infrastructure and a trained team of diabetes specialist , nurse and dietitian.7 Following 2010 according to American Diabetes association guidelines, the pump can be continued in an outpatient setting provided patients have the mental and physical capacity to do so. According to the International Diabetes federation guidelines, pump therapy should be considered only at the comprehensive care level, and in type 2 diabetes mellitus it should remain as a potential option in highly selected subjects.8
Suggested Insulin Pump Guidelines for India
Chronic kidney disease on dialysis or post- renal transplant patients.
In CKD there is a change in physiology of insulin metabolism and action. In such situation small doses of insulin can produce severe hypoglycemia . The patient is normally put on steroids and immunosuppressant, there is a rise in blood sugar value requiring high doses of insulin. In such patients who are on dialysis insulin requirement changes day by day , high immediately after dialysis and low on other days. With the help of insulin pump , CKD patients can manage blood glucose day by day and day after day with different basal profiles .
Continuous glucose monitoring patterns strongly suggesting the need for a variable basal insulin infusion rate
CGM pattern strongly indicates utilization of insulin pump therapy, patients can be advised to go in the same. The dawn phenomenon is clearly interpreted by CGM, can be easily resolved by changes in basal infusion profile of the pump.
Frequent travelers and those with untimely food habits
Insulin pump therapy offers complete flexibility in life style of those who are frequently travelling , who may be actively involved in job discussion and meeting with untimely food habits. In those who travelling from one time zone to another time zone smart pump offer the advantages of switching from one profile to another with the hit of a button.9
Contraindications
• Psychiatric illness10
• Absence of at least one responsible educated caregiver
• Lack of time to attend pump training sessions
• Blindness
• Affordability 11
Advantages of insulin pump therapy
• Improvement of HbA1c
• Reduction in blood sugar fluctuations
• Reduction in major and minor hypoglycemic episodes
• Improvement in neuropathic pain and sexual function
• Reduction in total daily dose of insulin
• Improvement in quality of life
• Insulin pump makes delivery of bolus insulin easier Insulin pump allows you to be flexible about when and what you eat
• Insulin pump eliminate the unpredictable effects of intermediate or long acting insulin
Disadvantages of insulin pump
• Cost of pump and consumables is beyond the reach of a common individual
• There is a risk of infection if the cannula is not changed once in every 3 days.
• Overeating and frequent blousing could result in weight gain and misuse of an insulin pump.
• Improper use of insulin pump bolus can lead to insulin stacking and low sugars.
• Insulin pump can cause diabetic ketoacidosis.
There are pluses and minuses to using a pump. Even though using an insulin pump has advantages and disadvantages , most pump users agree the advantages overweigh the disadvantages12
LITERATURE REVIEWS:
1. Leslie P .Plotnick, MD1, et al, The study conclude that insulin pump therapy in children and adolescents is safe and effective. There were fewer number of severe hypoglycemia and absolutely no increase in DKA visits with pump use. There was a fewer number of easily manageable site infections, none require surgical intervention. Also HbA1c increased with time on the pump, this appeared to be attributable to increasing age and duration of diabetes. Other words regardless of pump status, the glycemic control tend to loosen as diabetes duration increased and as children moved in to and through adolescence. After adjusting for the age and duration of diabetes HbA1c levels were lower on the pump.
2. Jothydev Kesavadev, M.D., 1et al. current studies have shown the benefits of CSII in T1DM as well as in T2DM. In developing countries like India, insulin pump therapy is fast growing up. The lack of reimbursement and insurance coverage has obstruct the use of pump to those who can afford to pay out of pocket. On the other hand, all signs point towards increasing affordability among patients in many emerging economies. However, it is not only just affordability, but also a multitude of factors that decide success in long-term therapy. Hence we have suggested guidelines to identify right candidates and exclude inappropriate indications.
3. Stephanie R.Johnson, et al, this study conclude that insulin pump therapy is associated with a markable improvement in glycemic control, which is sustained over many years. In cohort, this improvement was achieved with decreased rates of DKA and severe hypoglycemia, without an increase in BMI. Children and adolescents with poor glycemic control had the greatest reduction HbA1c with the pump therapy
4. C.Schreiver, U. Jacoby, B.watzer , A. Thomas,D.Haffner; The Paediatric patients with type 1 diabetes using a CSII presented with lower glycaemic variability and a concomitantly lower glycaemic risk parameter compared with those using MDII. Whether these findings translate into a lower risk of diabetes associated cardiovascular complications remains to be elucidated
5. M. Mavinkurve1 .A, et al, This review address the principles of insulin pump management in children which all health care professionals involved in caring for the child with diabetes, should be familiar with
6. Stuart A. Weinzimer, Joann H. A hern , Elizabeth A. Doyle et al. Insulin pump is a long term and effective by means of optimizing glycemic control in very young patients with type 1 diabetes and may be superior to multiple daily injections in reducing the risk of severe hypoglycemia in this age group. Employment of paid caregivers does not preclude safe and effective use of CSII.
7. Graham p. Leese, MD,Jixian Wang, PHD, Janice Broomhall, BSC, Paul Kelly, Andrew Marsden, et al.Hypoglycemia requiring emergency assistance from health service personnelis as common in people with type 2 diabetes treated with insulin as in people with type1 diabetes. It is associated with considerable NHS resource use that has a significant economic
8. . T. Danne & T. Battelino , P. Jarosz-Chobot ,O. Kordonouri & E. Pánkowska & J. Ludvigsson ,E. Schober ,et al. In conclusion, this study has shown that CSII provides convenient and flexible insulin delivery during routine treatment in many children and adolescents with type 1 diabetes. It has also highlighted the importance of frequent daily boluses and <50% basal insulin for good glycaemiccontrol, which is relevant to both CSII and multiple dose insulin therapy. A follow-up longitudinal study will investigate the long-term outcome in these patients.
9. Michel Joubert, MD,1 et al, in this retrospective study a high level of satisfaction in long-term CSII, giving a minimal discomfort .Safety and efficacy is maintained for many years of pump utilization, despite the minimal use advanced pump functions.
10. Pratik choudary, MD, 1 et al, This data suggest that LGS has the potential to reduce nocturnal hypoglycemia in patients with type1 diabetes at the highest risk. This is similar to results with insulin pump therapy providing the greatest reduction in hypoglycemia at baseline.
11. Larry A. Fox,MD,1et al, the data indicate that insulin pump therapy is safe and well adjusted in this population , consistent with three recent reports in these age group (10-12) . In our study, however CSII did not result in improved diabetic control when compared with insulin injection when compared with insulin injection.
12. Malgrozata Grazanka1, et al, The efficacy of CSII treatment observed in young T1DM adults was worse, compared to older patients. The reason for this remain unclear, it may be due simply to age- dependent behaviors, to the social environment or both. The younger group was characterized not only by lower SMBG frequency, and less frequent use of advanced insulin pump options, but also by a lower number of hypoglycemia per hundred measurements.
13. Jill Weissberg- Benchell, Ph.D, CDE1, et al, insulin pump therapy is associated with improved glycemic control compared with traditional insulin therapies (conventional therapy and multiple daily injections) and does not appear to be associated with significant adverse outcomes. Additional studies are needed to further examine the relative risk of CSII therapy, including the potential psychosocial impact of this technologically advanced therapy.
14. John Pickup, Martin Mattockand and Sally Kerry, conclude that insulin pump therapy is an effective form of insulin therapy for people with type 1 diabetes as glycemic control is slightly but significantly better than during optimized insulin injections. However we consider that in general insulin pump should be reserved for those with special problems such as unpredictable hypoglycemia or a marked increase in blood glucose concentration at dawn, despite best attempts to improve control with optimized injection regimens.
15. S. Shalitin M. Philip, Accumulating evidence suggests that insulin pump therapy is not only a feasible, safe and well accepted mode of therapy for pediatric T1DM patients, but also has proven to provide improved glycemic control and QOL , as compared with MDI, without any makeable greater risk. Reducing the risk of CSII entails the same interventions that promote safety in all T1DM patients : proper education , frequent blood glucose monitoring, attention to diet and exercise and the maintenance of communication with the diabetes team. The recipe for successful pump treatment must be tailored to each individual patient and all cases must have the continuing support of the experienced multidisciplinary diabetes team.
16. Mejedah M. Abdulrasoul 1* ,et al, CSII is safe and an effective mode of insulin delivery system in children and adolescents with T1DM. The usage of advanced features of the pump and CGM system will result glycemic control and reduce the frequency and duration of hypoglycemia . special attention and education regarding healthy eating habits is mandatory to avoid weight gain. Active involvement of the patients and their caregivers, accompanied with support from the medical team is needed to maximize the benefits of insulin pumps. Cost- effectiveness needs to be evaluated especially in areas with limited resources.
17. Richard M. Bergenstal, MD., et al, In both adults and children with inadequate controlled T1DM, sensor augmented pump therapy resulted in greater improvement in glycated hemoglobin levels, as compared with injection therapy. A greater proportion of both adults and children in the pump – therapy group than in the injection- therapy group reached the target glycated hemoglobin level.
18. Ruby Joshi Batajoo Catherime, and R. Messima Thomas A Wilson, This study shows that no continued long-term improvement in HbA1c of CSII over MDI. However, markable improvement is seen in older age group and those want more insulin per day , while the younger age group and those with less insulin requirement had relatively stable HbA1c during the study period. This study shown that compliance and motivation may play most important role as factors in diabetic control than different insulin regimens. Therefore, it is important to address these factors to patients and families while giving them a choice between different insulin regimens.
19. Roos Neuber1* et al, Within patient comparison suggest that metabolic control, frequency of severe hypoglycemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular with four daily insulin injection.
20. Jamie R. Wood , MD, et all, After an average of 3.8 years >80% of pediatric patient maintained pump therapy with baseline A1c. Patient discontinuing the pump were less adherent and did not achieve equivalent glycemic benefit compared with continued users ; these patient requires ongoing support aimed at improving adherence and outcomes.
21. Trang T. LY, MBBS, DCH, FRCP1,2,3 , et al, Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes.
22. Colleen S. Hughes, M.S.,1 et al, This article offers, for the first time, a method for smoothly reducing insulin delivery rate to prevent hypoglycemia in individuals with type 1 diabetes mellitus based on mathematically formal assessment of hypoglycemia risk. In silico, we demonstrate the way in this method can prevent hypoglycemia while avoiding hyperglycemia rebounds that exceed 180mg/dl.
23. Adrienne A. Nassar, MD1 , et al, Most patients using insulin pump can safely have their therapy transitioned when hospitalized. A policy on inpatient CSII use can be successfully implemented. Compliance with required procedures can be achieved , although there was a room to improve adherence with some process measures. Further study is needed to determine how to optimize glycemic control when pups are allowed during hospitalization.
24. Jessica M. Valenzuela,1 MS , Anna Mariya Patinno, 1 PHD, et al., present findings indicate that insulin pump therapy does not have negative implication for HRQOL. They also suggest that interventions aiming to improve HRQOL in this population should target child, parent and family adjustment and not focus solely on disease- related outcomes.
25. Stephanie R. Johnson, et al., We conclude that insulin pump therapy is associated with a significant improvement in glycemic control, which is sustained over many years. In our cohort, this improvement was achieved with reduced rates of severe hypoglycemia and DKA, without an increase in BMI. Children and adolescents with poor glycaemic control had the greatest reduction in HbA1c with insulin pump therapy.
26. Richard M. Bergenstal, M.D., David C . Klonoff M.D ., et al., This study showed that over a 3- month period the use of sensor-augmented insulin pump therapy with the threshold –suspended feature reduced noctumal hypoglycemia, without increasing glycated hemoglobin values.
27. Jennifer Sherr, MD and Willam V. Tamborlane, MD., CSII therapy has revolutionized diabetes care. With the findings of the DCCT, the importance of stringent glycemic control was identified. Since that time randomized and non-randomized studies have shown the efficacy of CSII across all age groups. Continuous glucose sensors are now changing the way that CSII therapy can improve control by decreasing glycemic excursions and manipulate insulin delivery to avoid otherwise asymptomatic hypoglycemia detected by these sensors. The endeavor of developing an artificial pancreas is transitioning from dream to reality as newer studies have demonstrated its use and effectiveness in small cohorts.
28. Jennifer L. Sherr Miladys Palau Collanzo,et al., This study was undertaken to evaluate whether 2-h suspensions of basal insulin due to artificially low sensor glucose values during the overnight period are safe in the absence of concurrent insulin pump or infusion site problems.
29. Bartlomiej Matejko1, Katarzyna Cyganek2 , et al., Results from this study indicate that the effectiveness and safety of insulin pump therapy is largely equivalent in younger and elderly T1DM patients . Basal/ bolus ratios in CSII treated patients were not significantly different between younger and older adult diabetic individuals. Patient over 50 years of age were willing to use advanced personal insulin pump options and tools such as dual- wave / square-bolus, Bolus Wizard and continuous glucose monitoring just as frequently as younger T1DM individuals.
30. Chiara Mameli, Andrea E. Scramuzza , et al., Insulin pump therapy is safe and effective in the pediatric population, and in this study, the major benefit in HbA1c was seen in males. The use of advanced pump features was associated with greater improvement in HbA1c. Future prospective studies would be useful to evaluate the reasons for differences observed among the three countries such as different dietary habits, lifestyle and pump education.
31. Francine Ratner Kaufman, MD, Mary Halvorson, RN, MNS, CDE, Sue Carpenter, RN, CDE, Debra , Devoe, MD, Our experience with insulin pump therapy in young children, as well as our entire population on CSII, has been extremely positive. Our young patients have had a reduction in HbA1c, mean blood glucose levels, and glycemic excursion; a decrease in episodes of severe hypoglycemia; and an increase in family functioning around diabetes. We believe the success of our pump program in young children can be attributed to the fact that we have employed appropriate criteria for patient selection and have a standardized method to initiate pump therapy and to follow and support our patients/families.
32. Pańkowska E1, Lipka M, Wysocka M, Szypowska A, Trippenbach-Dulska H, Czaplińska M, Kołodziejska B ,The method of continuous subcutaneous insulin infusion (CSII) provides good and sustained metabolic control in the youngest children with type 1 diabetes. Administering of that method from the very beginning of the diabetes treatment may decrease the risk of acute complications.
33. Shang-Ren Hsu 1 , Shi-Dou Lin 1*, et al., In conclusion, our experience has shown that insulin pump treatment results in a significant reduction in HbA1c ( by more than 1% ) that is sustainable for at least 3 years. Pump therapy may therefore be warrented when intermittent insulin injection fails to achieve treatment goals.
34. Raphael Del Roio Libertore Jr1and Duryal Damini2 Insulin pump therapy is safe and effective alternative for type 1 diabetes patients, resulting in improved metabolic control. Nevertheless, the greatest advantage of this therapeutic modality is the reduction in hypoglycemic events and the greater freedom in terms of lifestyle and eating habits, although the need capillary glucose measurements remain. The cost of insulin pump therapy is the highest among the therapeutic modalities available in the specific situations in which this treatment modalities cost-effective, it should be the therapy of choice
35. Hsin-Chieh Yeh, PhD; Todd T. Brown, MD, PhD; Nisa Maruthur, MD, MHS; Padmini Ranasinghe, MD, MPH et al. Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia.