The Glucose Sensing System A Basic Model
Blood glucose is the most effective physiological fuel stimulus of insulin secretion 3 . When the level of blood glucose increases, hormone secretion is enhanced with a characteristic dependency on the blood glucose level. A consensus minimal model delineating the manifold roles of glucose in insulin secretion by the P-cell has been developed. Those mechanisms are summarized schematically in Fig. 1, modified from a previous review 4 . Glucose stimulates insulin secretion by entry into P-cells...
Behavioral Strategies
All of these efforts are an attempt to raise the quality of standard care for people with diabetes. Since 1990 there has been a large focused effort to employ both diabetes education and behavioral strategy in order to improve outcomes. Increased follow-up care and comprehensive curricula are part of the trend. A meta-analysis by Roter 28 revealed that a combined educational behavioral focus is more effective than a single-focus intervention and that larger programs produced weaker effects. The...
Biological Significance Of The Vntr Region
A number of studies have suggested that the INS VNTR may have a biological role in the genetic regulation of insulin expression 70,157,158 . The proximity of this polymorphism to the INS transcriptional start site lt 400 bp upstream makes this an attractive hypothesis. Furthermore, an association between VNTR polymorphisms and human disease is not unprecedented. It has been suggested that the human HRAS1 gene, which encodes the H-ras protooncogene and is associated with a genetic susceptibility...
Defective Counterregulation
As described earlier, impaired hormonal responses to a decrease in blood glucose have been found to occur in adults with type 1 diabetes and manifest as either a diminished hormonal response and or an altered glucose threshold for hormone release these defects can be induced by exposure to antecedent hypoglycemia 73 and reversed by its elimination 76,77 . Defects in counterregulation have been found to occur after only one night of hypoglycemia 93 . This leads to delayed glucose recovery, which...
Secondary Prevention
Several trials have adopted the secondary prevention approach to delay or prevent the continued P-cell destruction in subjects that are currently euglycemic. In general, two separate agents are being studied in these trials nicotinamide and insulin. The rationale for using nicotinamide in intervention trials is based on animal models both the NOD mouse and the Bio-Breeding BB rat that nicotinamide prolongs remission, preserves P-cell function, and may prevent immune-mediated diabetes 79,80 ....
In How Many Ways Can the pCells Get Killed Killing by Virus
Since Yoon et al. 131 isolated coxsackie B4 virus from the pancreas of a patient with type 1 diabetes, various viruses have been studied to examine their diabetogenic potential and to what extent viruses represent an environmental factor that contributes to the disease. The viral infection seems to be able to indirectly activate autoreactive T-cells that, in turn, can generate initial pancreatic tissue damage. Damaged P-cells release previously ignored self antigens that may activate an...
Tertiary Prevention
The goal of tertiary prevention strategies is to induce a prolonged remission, allow for potential P-cell regeneration, and or preserve residual P-cell function, after the clinical onset of insulin deficiency. Trials using this approach have been largely unsuccessful. Early studies of immunosuppressive agents such as cyclosporin revealed that while administered, they prevented further loss of C-peptide secretion, resulting in improved metabolic function. Upon discontinuation, however, the...
REFERENCES Yyh
1. Venencie PY, Powell FC, Su WP, Perry HO. Scleredema a review of thirty-three cases. J Am Acad Dermatol 1984 11 128-134. 2. Grudeva-Popova J, Dobrev H. Biomechanical measurement of skin distensibility in scleredema of Buschke associated with multiple myeloma. Clin Exp Dermatol 2000 25 247-249. 3. Ikeda Y, Suehiro T, Abe T, et al. Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Intern Med 1998 37 861-864. 4. Hager CM, Sobhi HA,...
REFERENCES Mye
1. Currie CJ, Morgan CL, Peters JR. The epidemiology and cost of inpatient care for peripheral vascular disease, infection, neuropathy, and ulceration in diabetes. Diabetes Care 1998 21 42-48. 2. Morgan CL, Currie CJ, Stott NC, Smithers M, Butler CC, Peters JR. The prevalence of multiple diabetes-related complications. Diabet Med 2000 17 146-151. 3. Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry 1997 62 310-318. 4. Feldman EL, Stevens MJ, Greene DA....
Genetic Component
Severe diabetic retinopathy tends to run in families 20 and there is concordance among identical twins indicating that diabetic retinopathy has a genetic component. Several candidate gene or case-control studies have reported that there are genetic variations that are associated with an increased 21-25 or decreased 26 risk of diabetic retinopathy. This suggests that diabetic retinopathy is a genetically complex trait, meaning that there are genetic variations that increase susceptibility and...
Info Vdb
Note Because new component diseases tend to develop with age, exact prevalence figures for disease components give definite information only when given for specific age groups. Note Because new component diseases tend to develop with age, exact prevalence figures for disease components give definite information only when given for specific age groups. hypoparathyroidism and or mucocutaneous candidiasis. The component endocrine disorders are not known to be different in pathogenesis, pathology,...
Fluid and Electrolyte Losses
Fluid and electrolyte abnormalities are virtually universal in patients with DKA, and, if unrecognized or mismanaged, contribute significantly to the morbidity and mortality of DKA 1-6 . Fluid and electrolyte losses in DKA vary so that the extent of these losses is unpredictable in any given patient. However, estimates of losses that form the basis of the initial management of DKA have been formulated see Table 2 . It is emphasized that these recommendations are only guidelines, that each...
Fatty Acids As Insulin Secretagogues
Fatty acids trigger secretion of insulin in a glucose-dependent manner 3,44 . Fatty acids serve as an important endogenous fuel of islet tissue incubated with low glucose or in the absence of glucose. The possibility has been considered that a high level of fatty acids may inhibit the glucokinase glucose sensor because acyl-CoA, the first metabolite in fatty acid catabolism, is a very potent inhibitor of this enzyme 3 . However, this inhibition is competitive with glucose and is therefore...
Bardetbiedl Syndrome
Bardet-Biedl syndrome BBS is an autosomal recessive condition characterized by rod-cone dystrophy atypical retinitis pigmentosa , postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. Other features, not always present, include hepatic fibrosis, diabetes mellitus, reproductive abnormalities, endocrinological disturbances, short stature, developmental delay, and speech deficits. BBS is distinguished from the much rarer Laurence-Moon syndrome, in which...
Rhinocerebral Mucormycosis
Almost 50 of cases of rhinocerebral mucormycosis occur in patients with diabetes 31 . Fungi of the Rhizopus and Mucor species are the most common etiologic agents of this clinical entity. These fungi are ubiquitous saprophytic organisms, not uncommonly infecting the immunocompromised host 32 . Ketoacidosis temporarily disrupts host defense mechanisms, thereby permitting growth of Rhizopus oryzae. Such growth is inhibited by correcting acidosis 33 . These fungi have a predilection to invade...
SelfMonitoring of Blood Glucose
The most powerful monitoring tool is capillary blood glucose monitoring 46 . A small lancet pricks a patient's fingertip to obtain a small drop of blood that is placed on a testing strip. With electrochemical methods, the glucose concentration of this drop can be determined in 5 to 30 s. Patients with type 1 diabetes are encouraged to monitor blood glucose frequently. By determining glucose levels before a meal, patients can decide whether their insulin dose needs adjustment to counteract an...
Amount of Carbohydrate
Individuals with normal glucose tolerance experience a dose-related rise in postprandial blood glucose up to 60-75 g of carbohydrate consumed 4 . Consuming more carbohydrate does not increase blood glucose beyond 140 mg dL primarily because insulin secretion keeps up with entry of glucose into the blood. In type 1 diabetes, in which insulin secretion is absent or very low, the larger the dose of carbohydrate, the greater the blood glucose response. Studies in individuals with type 1 diabetes...
37zehrer Cl Gross Cr Comparison Of Quality Of Life Between Pancreas Kidney And
1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 329 977-986. 2. Rizza RA, Cryer PE, Gerich JE. Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after...
Landmark Clinical Trials Addressing the Management of Diabetic Retinopathy The
Numerous anecdotal reports throughout the 1960s suggested that photocoagulation provided some benefit in patients with PDR. To determine if this was the case and to better define the indications, side effects, long-term results, and complications of photocoagulation, a clinical trial, the Diabetic Retinopathy Study DRS , was commenced in 1971. The DRS demonstrated that scatter laser photocoagulation panretinal photocoagulation, PRP significantly reduced the risk of severe visual loss from PDR...
Scleredema
Although patients with this disorder develop induration hardening of the skin, scle-redema should not be confused with the distinctly different disease, scleroderma. The From Contemporary Endocrinology Type 1 Diabetes Etiology and Treatment Edited by M. A. Sperling Humana Press Inc., Totowa, NJ Fig. 1. Peau d'orange appearance of the upper back in a patient with scleroderma. The areas of involvement are firm to palpation. Fig. 1. Peau d'orange appearance of the upper back in a patient with...
Implantable Insulin Pumps
Insulin pumps that are totally implanted in the body and infuse insulin intravenously iv or intraperitoneally ip have been under development for some 20 yr 67-69 . However, unlike external pumps, they have yet to enter routine clinical practice, limited in large part by the relative invasiveness, cost, and occurrence of various complications. The advantages of implanted pumps include the pump being out of site and protected, the complete freedom from injection or insertion of a cannula needle,...
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Fig. 5. Hyperglycemia increases hexosamine pathway flux. In this pathway, increased O-linked Glc-NAc moieties on the transcription factor Sp1 increase its transactivating function and thus increase transcription of complications-associated genes Reproduced with permission from ref. 103. glycolysis to provide substrates for reactions that require urine diphosphate UDP -N-acetylglucosamine, such as proteoglycan synthesis and the formation of O-linked glycoproteins. Inhibition of the rate-limiting...
Grading of Diabetic Retinopathy and Implications for Clinical Practice
Current treatment recommendations for diabetic retinopathy are based on the results of the DRS and the ETDRS. Provided that careful follow-up can be maintained, the ETDRS recommended that patients with mild or moderate NPDR generally do not Mild NPDR At least one microaneurysm, but not as severe as moderate NPDR. The presence of mild NPDR has a 5 risk of progression to PDR within 12 mo and a 15 risk of progression to high-risk PDR within 5 yr. Moderate NPDR Extensive intraretinal hemorrhages...
REFERENCES Iqg
1. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 1922 12 141-146. 2. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 329 977-986. 3. Zinman B. The physiologic replacement of insulin an elusive goal. N Engl J Med 1989 321 363-370. 4....
Insulin Lispro Use During Pregnancy Possible Effects on the Fetus
Diamond and Kormas first questioned the safety of using insulin lispro during pregnancy in a letter to The New England Journal of Medicine in 1997 46 . They reported on two patients who used insulin lispro during pregnancies and deliveries. One of these pregnancies was terminated at 20 wk gestation and the second pregnancy resulted in a seemingly healthy infant after elective cesarean delivery, but who subsequently died unexpectedly 3 wk later. Both infants were discovered to have congenital...
Fat Replacers
Fat replacers or substitutes derived from modified proteins or carbohydrates were introduced into the market to assist in efforts to decrease total fat intake. Although this is theoretically possible, few studies have documented a health benefit. Most have been behavioral studies identifying that total fat, saturated fat, and dietary cholesterol intake can be reduced with the use of these products 53 . However, little change in energy intake or body weight has been reported. Persons with...
SUMMARY Pmu
Nutritional management of type 1 diabetes is dictated by prioritizing interventions that yield optimal metabolic outcomes and enhanced quality of life. The USDA Food Guide Pyramid continues to be the basis for a healthy diet providing vitamins, minerals, phytonutients, and fiber. Blood glucose control is best achieved with careful attention to adequately covering carbohydrate intake with insulin, generally utilizing carbohydrate-counting techniques. Although individuals with well-controlled...
IDDM Abg
provided by studies showing a significantly increased risk for first-degree relatives of affected individuals 18,19 . In addition, twin studies have revealed stronger disease concordance rates among monozygotic than dizygotic twins, although rates among monozygotic twins are less than 50 20 . In terms of specific genetic markers, type 1 diabetes is determined primarily by genes in the HLA region of chromosome 6. However, recent genome screens have identified at least 15 additional loci that may...
Islet Purification
Purification addresses the need to physically separate the islets from the surrounding nonendocrine acinar, vascular, ductal, and lymphoid tissue. Because there is a marked difference in density between endocrine and exocrine tissues, separation by density gradient centrifugation has evolved as the preferred method of purification. Purification is usually conducted on Eurocollins-Ficoll density gradients, in which the islets are centrifuged for a time sufficient to allow them to reach their...
Alstrom Syndrome
This syndrome was first described in 1959, when two of Alstrom's original patients died from renal failure 86 . The characteristic features of this syndrome appear to be pigmentary retinal degeneration, sensorineural hearing loss, childhood obesity, non-insulin-dependent diabetes mellitus, hyperlipidaemia, and chronic nephropathy. Features occasionally observed include acanthosis nigricans, hypogonadism, hypothyroidism, alopecia, short stature, and cardiomyopathy. A large kindred including...
Praderwilli Syndrome
Prader-Willi syndrome PWS is a complex, multisystem disorder first described in 1956 90 . It is diagnosed in about 1 in 10,000-15,000 people 91 , occurring in all sexes and races. Many of the manifestations are related to functional hypothalamic deficiency, and the clinical appearance in infancy differs markedly from that in childhood and adulthood 92 . The major features associated with PWS are decreased fetal activity, neonatal hypotonia and feeding difficulties, hyperphagia with obesity, and...
Mononeuropathies of the Extraocular Muscles
Palsies involving the third oculomotor , fourth superior oblique , and sixth abducens lateral rectus cranial nerves occur not uncommonly in diabetes. However, despite this definite association, one must always bear in mind the potential for other pathology, including possible life-threatening disease 50 . Palsies of the third and sixth nerves are more commonly the result of diabetes than fourth-nerve palsies, so the latter should never be attributed to diabetes without a thorough investigation...
Summary Of The Overall Dcct Results
The DCCT ended the controversy as to whether the degree of metabolic control of type 1 diabetes influences the development of long-term complications 14 . The DCCT was a prospective randomized trial that compared the effects of intensive treatment IT with those of conventional treatment CT on retinopathy, nephropathy, and neuropathy in subjects with type 1 diabetes. IT was aimed at producing normoglycemia preprandial blood glucose levels of 70-120 mg dL, HbA1c lt 6.0 and consisted of MDI three...
CONCLUSION Wdv
There are many unresolved questions regarding the etiology, sequelae, and prevention of this common acute complication of the treatment of type 1 diabetes. Definitions of good glycemic control that do not include a statement about absence of problematic hypoglycemia are incomplete and inadequate. The benefits of long-term good glycemic control cannot be gainsaid, but further progress in the application of intensified diabetes therapy needs to be made before it can be safely applied to all...
Type 1 Diabetes References
1. Last JM. A Dictionary of Epidemiology. Oxford University Press, New York 1983. 2. World Bank. The World Bank overview. In World Development Report 1993. Oxford University Press, Oxford, 1993, pp. 1-16. 3. World Health Report 1999. 4. LaPorte RE, Tajima N, Akerblom HR, et al. Geographic differences in the risk of insulin-dependent diabetes mellitus the importance of registries. Diabetes Care 1985 8 Suppl 1 17-23. 5. Diabetes Epidemiology Research International Group DERI . Geographic patterns...
Malignant Otitis ExternaInvasive Otitis Externa
This potentially life-threatening condition occurs in elderly diabetic patients and involves the external auditory canal and skull. Pseudomonas aeruginosa is the most common etiologic agent. However, it has also been described secondary to colonization of the external ear canal by Aspergillus species 28 . Presenting clinical features include ear discharge, severe pain, and hearing impairment, often in the absence of fever. Examination of the auditory canal shows edema, intense cellulitis, and...
Insulin Requirements
Women with type 1 diabetes must increase their insulin dosage to compensate for these diabetogenic forces of normal pregnancy. Table 3 shows that insulin requirements increase until wk 32, at which time they stabilize until the end of term. The exact pattern of insulin dosage requirement, however, is still controversial. Many observers have detected a decline in insulin requirement in late first trimester of diabetic pregnancies 38 . Others have shown no changes 39,40 or an increase 41-43 ....
Beneficial Effects On Glycemic Control
As opposed to exogenous insulin-based therapy, successful pancreas transplantation reliably restores endogenous insulin secretion and uniquely maintains glucose levels in the normal range without significant hypoglycemia for many years. Many investigators have detailed the beneficial effects of pancreas transplantation on insulin secretion and carbohydrate metabolism. In a study of 96 pancreas-transplanted patients, fasting plasma glucose, hemoglobin A1c, glucose-induced insulin secretion, and...
Support Strategies
Clinical strategies aimed at improving diabetic control throughout adolescence have focused largely upon psychosocial support rather than clinical care. There is some evidence, however, that diabetic control is unlikely to improve from late childhood to late adolescence, and we have advocated that diabetic control needs to be optimal prior to the advent of adolescence 52 . Furthermore, research in our clinic has supported the notion that early adjustment to insulin-dependent diabetes mellitus...
Waxy Skin And Stiff Joints Cheiroarthropathy
In the dermatologic literature, the descriptive term waxy skin and stiff joints appears more commonly than the term cheiroarthropathy. The most common site of cutaneous involvement is the hands and, like scleredema, it can sometimes be confused with scleroderma. Clinically, the skin on the dorsal surface of the hands is waxy in appearance and somewhat taut 6 . A simple screening test is to ask the patient to bring his or her hands together with the palmar surfaces apposed as if one were about...
Clinical Features of Diabetic Retinopathy
Retinal hemorrhages are a common feature of diabetic retinopathy and vary in their appearance based on their location within the retina. The superficial capillary bed is located in the nerve fiber layer and hemorrhages from superficial capillaries have a flame-shaped appearance as the blood spreads between nerve fibers that run parallel to the retinal surface. Hemorrhages occurring from the deep capillary beds, where the arrangement of cells is perpendicular and more compact, tend to be...
The Process of Transition and the Eventual Transfer to Adult Care
In due course, the adolescent with diabetes who has been cared for in a pediatric environment, whether privately by a pediatric endocrinologist or in a pediatric clinic, must transfer care to an adult environment. The question of when and how will depend on a number of factors, including the perceived readiness of the young person, the availability of appropriate adult services, and the general policy of a hospital or clinic service. Most studies have suggested that from an adolescent's point...
Acquired Perforating Dermatosis
The perforating disorders are a group of cutaneous diseases that share a common phenomenon the outward elimination of dermal contents via claws formed by downgrowths of the epidermis. Clinically, actual plugs of degenerated collagen and elastin admixed with keratin are seen perforating through the epidermis to the surface of the skin. The primary systemic disease associated with perforating disorders is chronic renal failure CRF in particular, CRF resulting from diabetes mellitus. Occasionally,...
Urinary Tract Infection
Urinary tract infection UTI is commonly encountered in patients with diabetes 9 . However, studies have failed to demonstrate significant differences in epidemiological, clinical, and microbiological features of UTI in patients with or without diabetes except for a relative difficulty in eradicating infection in the former group 10 . Asymptomatic bacteruria occurs with a higher frequency one study demonstrated a 26 incidence in diabetic women compared to 6 in controls 11 . Whether this increase...
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The HLA class II DPB1 locus see Fig. 1 may also influence susceptibility to T1DM. Analysis of 269 multiplex families from the Human Biological Data Interchange suggest that HLA-DPB 1 0301 and HLA-DPB1 0202 alleles are predisposing for T1DM, whereas HLA-DPB1 0402 appears protective 115 . Interestingly, the effect of the class II locus DPB1 appears to be more apparent in patients with this genotype than in patients carrying the highest-risk DR3 DR4-DQB1 0302 genotype 115 . Fig. 6. The human TCR...
Activation of Protein Kinase C
Protein kinase Cs PKCs are a family of at least 11 isoforms, 9 of which are activated by the lipid second-messenger diacylglycerol DAG . Intracellular hyper-glycemia increases DAG content in cultured microvascular cells and in the retina and renal glomeruli of diabetic animals 79-81 . Intracellular hyperglycemia appears to increase DAG content primarily by increasing its de novo synthesis from the glycolytic intermediate glyceraldehyde-3-phosphate via reduction to glycerol-3-phosphate and...
Assessment
Treatment of a diabetic foot ulcer begins with assessment of neuropathy and arterial occlusive disease by history and physical examination. There may be a history suggesting generalized atherosclerosis. These patients often have coronary artery disease and cerebrovascular disease, as well as peripheral vascular disease. Many patients have a history of claudication 9 . Some have had a prior amputation. A detailed evaluation of pulses will determine the degree and location of atherosclerotic...
Info Bcr
Calcium to intake of 1000-1200 mg d Abbreviations LDL, low-density lipoprotein SFA, saturated fatty acid PUFA, polyunsaturated fatty acid MUFA, monounsaturated fatty acid CVD, cardiovascular disease USDA, United States Department of Agriculture. Abbreviations LDL, low-density lipoprotein SFA, saturated fatty acid PUFA, polyunsaturated fatty acid MUFA, monounsaturated fatty acid CVD, cardiovascular disease USDA, United States Department of Agriculture. a classic study illustrating this point,...
Orthostatic Hypotension
The first step in the management of orthostatic hypotension is the discontinuation, where possible, of long-acting hypotensive agents that may be contributing to the problem. Occasionally, the patient can be switched to a shorter-acting agent captopril, e.g. and the timing of the dose altered in order to minimize daytime orthostatic changes. Other non-neuropathic etiologies such as volume depletion, adrenal insufficiency, anemia, and hypothyroidism should be addressed. Typical initial...
Management Of Patients With Type Diabetes During Surgery
Optimal management of diabetes during surgery requires reliable, frequent blood glucose monitoring as well as timely and appropriate insulin replacement to maintain blood glucose in an acceptable range while avoiding ketoacidosis. The actual regimen adopted depends on the nature of the surgical procedure, expected duration of fasting, as well as the pre-existing insulin regimen. For example, for a patient using an MDI program who is due to undergo cataract extraction, diabetes could be managed...