Keith G. Dawson

Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada

OBJECTIVES To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Associations recommended targets in ambulatory patients with type 2 diabetes. METHODS Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success - defined as the achievement of a blood pressure (BP) of 13080 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmolL and total cholesterolhigh-density lipoprotein cholesterol ratio lower than 4.0 - are reported. RESULTS Overall, 46% of individuals had a BP that was above the Canadian Diabetes Associations recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose- lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterolhigh-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C. INTERPRETATION A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence- based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.

Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy.

Background. Diabetic retinopathy is a major complication of type 1 diabetes and remains a leading cause of visual loss. There have been no comparisons of the effectiveness of intensive medical therapy and islet cell transplantation on preventing progression of diabetic retinopathy. Methods. The British Columbia islet transplant program is conducting a prospective, crossover study comparing medical therapy and islet cell transplantation on the progression of diabetic retinopathy. Progression was defined as the need for laser treatment or a one step worsening along the international disease severity scale. An interim data analysis was performed after a mean 36-month follow-up postislet transplantation and these results are presented. Results. The medical and postislet transplant groups were similar at baseline. Subjects after islet transplantation had better glucose control than the medically treated subjects (mean HbA1c 6.7%±0.9% vs. 7.5±1.2, P<0.01) and were C-peptide positive. Progression occurred significantly more often in all subjects in the medical group (10/82 eyes, 12.2%) than after islet transplantation (0/51 eyes, 0%) (P<0.01). Considering only subjects who have received transplants, progression occurred in 6/51 eyes while on medical treatment and 0/51 posttransplant (P<0.02). Conclusions. Progression of diabetic retinopathy was more likely to occur during medical therapy than after islet cell transplantation.

Evaluation of a mobile diabetes care telemedicine clinic serving Aboriginal communities in northern British Columbia, Canada

Introduction. In British Columbia, Aboriginal diabetes prevalence, hospitalization and mortality rates are all more than twice as high as in the rest of the population. We describe and evaluate a program to improve access to diabetes care for Aboriginal people in northern communities. Study design. Cost-effectiveness evaluation. Methods. A diabetes nurse educator and an ophthalmic technician travel to Aboriginal reserves, offering people with diabetes services recommended in current clinical practice guidelines: retinopathy screening by digital retinal fundus photography, glaucoma screening by tonometry, point-of-care urine and blood testing to detect microalbuminuria and dyslipidemia and to measure glycated hemoglobin, foot examinations and foot care advice, blood pressure and height and weight measurement and diabetes care advice. Via electronic communication, an ophthalmologist and an endocrinologist in Vancouver review the findings and supervise the mobile clinic staff. Results. During the first year, 25 clinics were held at 22 sites, examining 339 clients with diabetes. Exit surveys showed high levels of client satisfaction. Mean cost per client (Cdn

Canadian Ophthalmological Society evidence-based clinical practice guidelines for the management of diabetic retinopathy

1,231) was less than for the alternative, transporting clients to care in the nearest cities (Cdn

Canadian Ophthalmological Society Evidence-based Clinical Practice Guidelines for the Management of Diabetic Retinopathy - executive summary.

1,437). Conclusions. The mobile clinic is cost-ef-fective and improves access to the recommended standard of diabetes care.

Endocrine Physiology of Electrolyte Metabolism

The objective of this document is to provide guidance to Canadian ophthalmologists regarding screening and diagnosis of diabetic retinopathy (DR), management of diabetes as it pertains specifically to DR, and surgical and nonsurgical approaches to the treatment of DR. These guidelines apply to all Canadians with type 1 or type 2 diabetes of all ethnic origins. Other health professionals involved in the care of people with diabetes may find this document helpful. These guidelines were systematically developed and based on a thorough consideration of the medical literature and clinical experience. These guidelines are not meant or intended to restrict innovation. Guidelines are not intended to provide a “cookbook” approach to medicine or to be a replacement for clinical judgment; rather, they are intended to inform patterns of practice. Adherence to these guidelines will not necessarily produce successful outcomes in every case. Furthermore, these guidelines should not be used as a legal resource, as their general nature cannot provide individualized guidance for all patients in all circumstances. Guidelines are not intended to define or serve as a legal standard of medical care. Standards of medical care are specific to all the facts or circumstances involved in an individual case and can be subject to change as scientific knowledge and technology advance, and as practice patterns evolve. There is no expectation that these guidelines be applied in a research setting. No comment is made on the financial impact of procedures recommended in these guidelines. Ideally, guidelines are flexible tools that are based on the best available scientific evidence and clinical information, reflect the consensus of professionals in the field, and allow physicians to use their individual judgment in managing their patients. These guidelines

Mobile diabetes telemedicine clinic (MDTC): role in first nations care and treatment

The Canadian Ophthalmological Society Evidence-based Clinical Practice Guidelines for the Management of Diabetic Retinopathy were developed to provide guidance to Canadian ophthalmologists regarding the management of diabetic retinopathy (DR). Readers are directed to the full guideline document, available online at http://www. canadianjournalofophthalmology.ca/, for more detail and references.

Agreement of Point-of-Care Capillary Glycated Hemoglobin Levels with Conventional Screening Tests for Diabetes Mellitus in a Canadian First Nations Population

SummaryHistorically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions.Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and pros-taglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by β1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II.Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified nalriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide).Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure.Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion.Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected.The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.RésuméClassiquement, l’ion sodium s’est vu attribué la première place, voire une place exclusive par rapport au autres ions, dans la pathologie cardiovasculaire. Récemment, d’autres ions tels que le chlore, le potassium, le magnésium et le calcium ont trouvé leur place dans les mécanismes de l’hypertension, les arythmies cardiaques et les désordres métaboliques. On s’est de même intéressé aux commandes endocriniennes de l’équilibre ionique qui impliquent des actions hormonales classiques mais aussi des phénomènes de neurotransmission et des effets cellulaires inhabituels d’hormones endocrines.Des études montrent que le contrôle du système rénine-angiotensine-aldostérone dépend non seulement du taux de calcium dans le cytosol mais aussi de la présence de l’ion chlore et des prostaglandines dans la macula densa. La libération de rénine est stimulée par l’hyperpolarisation des cellules juxtaglomérulaires induite par les agonistes β1, la parathormone, le glucagon, le magnésium et une faible concentration du cytosol en calcium. La libération de rénine est inhibée par des concentrations élevées de calcium, potassium et angiotensine II.Faisant suite à la libération de rénine, la régulation hormonale stimule l’activité de l’enzyme de conversion par le cortisol et les prostaglandines (PGE2). Joue aussi un rôle dans le contrôle hormonal l’hormone antidiurétique, qui provoque une dilution des électrolytes extracellulaires et augmente les résistances périphériques. Un facteur natriurétique récemment isolé de l’oreillette semble avoir une action diurétique du même type que celle du furosémide.Le rôle des autres électrolytes a été soigneusement examiné. Le chlore peut être déterminant dans la réabsorption rénale de sodium en fonction des taux plasmatiques des prostaglandines. Le calcium est un régulateur indispensable de la sécrétion d’adrénaline, de rénine, d’aldostérone. De même, les variations de l’ion calcium servent à la contraction musculaire lisse. Sa concentration dans l’organisme est réglée par la parathormone et la vitamine D. De plus, une alimentation riche en calcium joue un rôle protecteur contre l’hypertension, tandis que les inhibiteurs calciques diminuent la pression artérielle.Les systèmes endocriniens jouent un rôle capital dans la protection contre l’élévation brutale de la kaliémie par le biais de l’insuline et de la modulation adrénergique de la distribution extrarénale du potassium. Il est admis que l’aldostérone est la mécanisme de régulation retardée de l’excrétion de potassium.Les concentrations de magnésium chutent en cas d’hyperaldostéronisme, d’hyperparathyroïdisme et d’acidocétose diabétique ainsi que de malnutrition. Si une hypokaliémie coexiste, elle peut rester réfractaire tant que l’hypomagnésémie n’est pas corrigée.L’ensemble de ces actions hormonales et électrolytiques sont donc un élément important de régulation du système cardiovasculaire.ZusammenfassungHistorisch stand das Natrium-Ion in bezug auf kardiovaskuläre Erkrankungen, vielleicht andere Ionen ausschlieβend, im Vordergrund. In letzter Zeit fanden andere Ionen, wie Chlorid, Kalium, Magnesium und Kalzium, steigende Beachtung hinsichtlich Hypertonie, Herzarrhythmien und metabolischer Störungen. Endokrine Faktoren, die diese Ionen kontrollieren, fanden ebenfalls zunehmende Beachtung; zu ihnen zählen klassische Hormonwirkungen ebenso wie die Neurotransmission und parakrine hormonelle Wirkungen.Studien zeigen, daβ die Kontrolle des Renin-Angiotensin-Aldosteronsystems durch die Kalziumspiegel im Cytosol der juxtaglomerulären Zellen ebenso wie durch Chloridionen und Prostaglandine in der Macula densa erfolgt. Die Renin-Freisetzung wird durch eine durch β1-Agonisten, Nebenschilddrüsenhormon, Glukagon, Magnesium und erniedrigtes Cytosol-Kalzium induzierte Hyperpolarisation der juxtaglomerulären Zelle stimuliert. Die Freisetzung von Renin wird durch erhöhtes Kalzium, Kalium und Angiotensin II gehemmt.Der Reninfreisetzung folgend, umfaβt die Hormonregulation die Stimulation der Converting-Enzym-Aktivität durch Kortison und Prostaglandin (PGEz). Zu anderen hormonellen Kontrollmechanismen zählt das anti-diuretische Hormon, das eine Verdünnung der extrazellulären Elektrolyte und eine Erhöhung des peripheren Widerstandes bewirkt. Ein kürzlich identifizierter, aus Vorhofkammern isolierter natriuretischer Faktor, scheint ein potentes Diuretikum mit Furosemid-ähnlichen Wirkungen zu sein.Andere Elektrolyte wurden genauer untersucht. Chlorid kann eine dominierende, Prostaglandin-abhängige Rolle für die rénale Natrium-Reabsorption spielen. Kalzium wurde als grundlegender Regulator von Hormonen wie Noradrenalin, Renin und Aldosteron erkannt. Ebenso sind Änderungen der Kalziumionenkonzentration das Mittel, durch das Kontraktion glatter Muskeln beeinfluβt wird. Nebenschilddrüsenhormon und Vitamin D regulieren die Spiegel dieses Ions im Körper. Zusätzlich scheint eine hohe Kalziumaufnahme mit der Nahrung eine protektive Rolle gegen Bluthochdruck zu spielen, während Kalziumantagonisten den Blutdruck reduzieren.Das endokrine System besitzt eine wichtige Schutzfunktion in bezug auf akute Erhöhungen des Serum-Kaliums; mit Hilfe von Insulin und der adrenergen Modulation kann Kalium extrarenal aus dem Serum entfernt werden. Aldosteron wurde als verzögerter Regulator der Kaliumausscheidung erkannt.Magnesiumspiegel sinken bei Hyperaldosteronismus, bei Hyperparathyreose und Ketoazidose ebenso wie bei Mangelernährungszuständen. Ein begleitender Kaliummangel kann therapierefraktär sein, bis die Hypomagne-siämie korrigiert ist.Die integrierte Wirkung dieser Hormone und Elektrolyte kann daher für die Regulation des kardiovaskulären Systems von gröβter Wichtigkeit sein.SommarioStoricamente è stata data una grande importanza allo ione sodio in relazione alle malattie cardiovascolari, forse accantonando gli effetti di altri ioni. Recentemente è stata posta un’attenzione sempre maggiore su altri ioni, fra cui il cloro, il potassio, il magnesio ed il calcio, in relazione all’ipertensione, alle aritmie cardiache e alle alterazioni metaboliche. Anche i fattori endocrini che controllano questi ioni sono stati fatti oggetto di una crescente attenzione, e fra essi ricordiamo i classici effetti degli ormoni, gli effetti dei neurotrasmettitori e gli effetti secondari degli ormoni stessi.Alcuni studi suggeriscono che il controllo del sistema renina-angiotensina-aldosterone è influenzato dai livelli di calcio nel cito-plasma delle cellule iuxtaglomerulari e dai livelli di cloro e di prostaglandine nella macula densa. La liberazione di renina è stimolata dall’iperpolarizzazione delle cellule iuxtaglomerulari indotta dai β-1-agonisti, dall’ormone paratiroideo, dal glucagone, dal magnesio e da bassi livelli di calcio citoplasmatico. La liberazione di renina è inibita da elevati livelli di calcio, di potassio e di angiotensina II.Successivamente alla liberazione di renina, la regolazione ormonale include la stimolazione dell’attività dell’enzima di conversione da parte del cortisolo e delle prostaglandine (PGE2). Fra gli altri controlli ormonali ricordiamo l’ormone antidiuretico, che détermina una diluizione degli elettroliti extracellulari ed un aumento delle resistenze periferiche. Un fattore natriuretico di recente identificazione, isolato dagli atri cardiaci, sembra agire come potente diuretico, con effetti simili a quel

The economic cost of diabetes in Canada, 1998

| 195 one of the PD.SHR4 strains showed highest concentrations of LDL cholesterol compared both to PD and the other PD.SHR4 congenic. Both PD.SHR4 strains had smaller LDL particle sizes and lower HDL cholesterol than PD. The expression profile revealed systematic dysregulation of transcription around insulin gene network node and in number of genes constituting circadian rhytmicity pathway (Arntl, Clock, Nfil3, PER2 and PER3) in PD.SHR4. Discussion/conclusion: The introduction of chr.4 region of SHR origin including defective Cd36 into BN-Lx and PD genetic backgrounds resulted in disconnected changes in metabolic profile and its reaction to pharmacological challenge. The eventual phenotypic outcome of deleterious mutation is thus a function of complex interactions between environment and genomic background, upon which it operates. Genetics of type 2 diabetes No conflict of interest

Type 2 Diabetes Mellitus Management in Canada: Is It Improving?

OBJECTIVES 1) How closely do capillary glycated hemoglobin (A1C) levels agree with venous A1C levels? 2) How well do venous A1C levels agree with plasma glucose for diagnosis of diabetes in this population? METHODS The Seabird Island mobile diabetes clinic screened people not known to have diabetes by using finger-prick capillary A1C levels with point-of-care analysis according to the Siemens/Bayer DCA 2000 system. Clients then went to a clinical laboratory for confirmatory testing for venous A1C levels, fasting plasma glucose (FPG) and plasma glucose 2 hours after 75 g oral glucose load (2hPG). A reference laboratory compared the DCA 2000 and the clinical laboratorys Roche Integra 800CTS system to the National Glycohemoglobin Standardization Program Diabetes Control and Complications Trial (DCCT) reference. RESULTS 1) In the reference laboratory, DCA 2000 and Integra 800CTS both agreed very closely with the DCCT standard. In the field, capillary glycated hemoglobin percent (A1C) % was biased, underestimating venous A1C % by a mean of 0.19 (p<0.001). The margin of error of bias-adjusted capillary A1C % was ±0.36 for 95% of the time, compared to ±0.27 for venous A1C%. 2) By linear regression, we found FPG 7.0 mmol/L and 2hPG 11.1 mmol/L predicted mean venous A1C levels very close to 6.5%, with no significant bias. CONCLUSIONS Point-of-care capillary A1C did not perform as well in the field as in the laboratory, but the bias is correctible, and the margin of error is small enough that the test is clinically useful. In this population, venous A1C levels ≥6.5% agree closely with the FPG and 2hPG thresholds to diagnose diabetes; ethnic-specific adjustment of the venous A1C threshold is not necessary.