Pharmacological therapy of diabetes in the elderly - old, new and very new drugs Dr. med. Dr. Univ. Rome Andrej Zeyfang Bethesda Hospital Stuttgart University of Ulm Germany 1

Geriatric giants + Food + Drinking Interaction Diabetes - Syndromes Immobility Inkontinence Intellectual decline Instability Iatrogenic damage + Food + Drinking Den bekannten 5 ger. Is muss heute noch ein 6. dazugestellt werden... Interaction Diabetes - Syndromes

Diabetes in old age Diabetes in old age concerns a heterogeneous group of patients, all diabetics seen below are at the age of 75 years …

Volume 13, Issue 6, Pages 497-502 (July 2012) Diabetes Mellitus in Older People: Position Statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes Alan Sinclair, MSc, MD, FRCP, John E. Morley, MB, BCh, Leo Rodriguez-Mañas, MD, PhD, Giuseppe Paolisso, MD, PhD, Tony Bayer, MB, FRCP, Andrej Zeyfang, Dr Med, Dr Univ (Rome), Isabelle Bourdel-Marchasson, MD, PhD, Ulrich Vischer, MD, Jean Woo, MD, FRCP, Ian Chapman, MBBS, PhD, FRACP, Trisha Dunning, AM, RN, MEd, PhD, Graydon Meneilly, MD, FRCPC, FACP, Joel Rodriguez-Saldana, MD, PhD, Luis Miguel Gutierrez Robledo, MD, PhD, Tali Cukierman-Yaffe, MD, MSc, Roger Gadsby, MD, Guntram Schernthaner, MD and Kate Lorig, RN, DrPH JAMDA Volume 13, Issue 6, Pages 497-502 (July 2012) DOI: 10.1016/j.jamda.2012.04.012 Copyright © 2012 American Medical Directors Association, Inc. Terms

Volume 13, Issue 6, Pages 497-502 (July 2012) No patient should commence glucose lowering therapy with drugs until the fasting glucose level is consistently 7 mmol/l or higher: ‘Not before 7’ To reduce the risk of hypoglycaemia, no patient should have a fasting glucose on treatment of <6.0 mmol/l: ‘Not below 6’ Low blood glucose states (levels of glucose of <5.0 mmol/l) should be strictly avoided JAMDA Volume 13, Issue 6, Pages 497-502 (July 2012) DOI: 10.1016/j.jamda.2012.04.012 Copyright © 2012 American Medical Directors Association, Inc. Terms

HbA1c 7,5% n=28.000 patients with T2DM Metformin Insulin Diabetes: Niedriger HbA1c als Sterberisiko Cardiff – Zu anspruchsvolle Ziele in der Blutzuckerkontrolle scheinen Typ2-Diabetikern eher zu schaden. Zu diesem Ergebnis kommt eine Analyse von Krankenakten britischer Hausärzte im Lancet (2010; doi: 10.1016/S0140-6736(09)61969-3). Dort stieg die Sterblichkeit der Patienten, wenn die HbA1c-Konzentration auf Werte gesenkt wurde, die unter Diabetologen bis vor kurzem als besonders wünschenswert eingestuft wurden. Gesunde Menschen haben einen HbAa1c-Wert von unter 6 Prozent. Bei Diabetikern kann er, wenn der Blutzucker schlecht eingestellt ist, auf 10 Prozent oder höher steigen. Auch unter der Therapie bleibt er bei vielen Diabetikern bei über 8 Prozent. Mit einer 7 vor dem Komma sind viele Patienten glücklich, Diabetologen forderten aber bisher die Normalisierung. So auch in der ACCORD-Studie. Dort hatten die Ärzte bei der Hälfte der Typ-2-Diabetiker ein HbA1c-Ziel von unter 6 Prozent ausgegeben. Am Ende erreichten die Patienten 6,4 Prozent. Doch die erhofften Vorteile blieben aus. Die Studie wurde vorzeitig abgebrochen, weil die Sterblichkeit unter der intensiven blutzuckersenkenden Therapie signifikant höher war als in der Vergleichsgruppe, die immerhin einen HbA1c-Wert auf 7,5 Prozent geschafft hatten. Seither wird über die Ursachen spekuliert. Neben der Auswahl der Medikamente (mehr als 90 Prozent hatten Kombinationen mit Rosiglitazon erhalten, das im Verdacht steht das Herzinfarktrisiko zu erhöhen) wird eine erhöhte Zahl von Hypoglykämien für die Ergebnisse verantwortlich gemacht. Jetzt kommt eine Analyse der General Practice Research Database zu ähnlichen Ergebnissen. Die Datenbank sammelt die Krankenakten britischer Patienten. Darunter befinden sich auch 48.000 Typ-2-Diabetiker, die Craig Currie von der Universität Cardiff in zwei Gruppen einteilte. Die erste Kohorte bestand aus 27.965 Patienten. Bei ihnen war die orale Therapie von einer Monotherapie auf eine Kombination mit Metformin und einem Sulfonylharnstoff intensiviert worden. zum Thema Abstract der Studie General Practice Research Database ACCORD-Studie Im Zehntel der Patienten mit der besten Blutzuckerkontrolle wurde ein HbA1c-Wert von etwa 6,5 Prozent erreicht. Doch wie in der ACCORD-Studie war die Sterblichkeit dieser Patienten höher als bei Patienten, bei denen der HbA1c-Wert etwa 7,5 Prozent betrug. Hier lag der niedrigsten Punkt einer U-förmigen Kurve: Bei höheren HbA1c -Werten stieg die Sterblichkeit wieder an. Ein ähnliches Phänomen ermittelte Currie für die zweite Kohorte von 20.005 Typ-2-Diabetikern. Diese Patienten hatten begonnen Insulin zu spritzen, entweder oder anstelle der oralen Antidiabetika oder zusätzlich zu ihnen. Erneut war die Sterblichkeit der Patienten, die den HbA1c -Wert auf etwa 7,5 Prozent senkten, am niedrigsten. Sie stieg nach beiden Seiten der U-Kurve an: Wie in der ersten Kohorten hatten Patienten mit einem nahezu idealen HbA1c -Wert von 6,5 Prozent eine gleich hohe Sterblichkeit wie Patienten mit einem aus diabetologischer Sicht katastrophalen HbA1c -Wert von über 10 Prozent. Die Ergebnisse verstärken die Bedenken, die nach der ACCORD-Studie geäußert wurden, auch wenn eine retrospektive Datenbankanalyse keine Kausalität herstellen kann, wie Beverley Balkau vom INSERM-Institut in Villejuif/Frankreich und Dominique Simon von der Groupe Hospitalier Pitie Salpetriere in Paris im Editorial anmerken (Lancet 2010; doi:10.1016/S0140-6736(09)62192-9). Auf der anderen Seite gibt die Datenbankanalyse allerdings die derzeit vorherrschende Behandlungsrealität unter Umständen besser wieder als die kontrollierte ACCORD-Studie, in der ausgesuchte Patienten unter Idealbedingungen betreut wurden. Die Ursache der vermehrten Todesfälle bleibt weiter im Dunkeln. Viele Diabetologen dürften sie in vermehrten Hypoglykämien vermuten und eine intensive blutzuckersenkende Therapie deshalb mehr noch als bisher von der regelmäßigen Blutzuckerselbstmessung durch den Patienten abhängig machen. © rme/aerzteblatt.de C.J. Currie et al.: Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. The Lancet, Volume 375 (2010), 481 - 489.

Depiction of the elements of decision-making used to determine appropriate efforts to achieve glycaemic targets. Greater concerns about a particular domain are represented by increasing height of the ramp. Thus, characteristics/predicaments towards the left justify more stringent efforts to lower HbA1c, whereas those towards the right are compatible with less stringent efforts. Where possible, such decisions should be made in conjunction with the patient, reflecting his or her preferences, needs and values. This ‘scale’ is not designed to be applied rigidly but to be used as a broad construct to help guide clinical decisions. Adapted with permission from Ismail-Beigi et al [ref 20] Figure 1 Inzucchi SE et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2012 Jun;35(6):1364-79.

T2DM Antihyperglycemic Therapy: General Recommendations If the A1c target is not achieved after ~3 months, consider one of the 5 treatment options combined with metformin (dual combination): a sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 receptor agonist or basal insulin. Note that the order in the chart is determined by historical introduction andr oute of administration and is not meant to denote any specific preference. Choice is based on patient and drug characteristics, with the over-riding goal of improving glycemic control while minimizing side effects. Shared decision-making with the patient may help in the selection of therapeutic options. Rapid-acting secretagogues (meglitinides) may be used in place of sulfonylureas. Consider in patients with irregular meal schedules or who develop late postprandialhypoglycemia on sulfonylureas. Other drugs not shown (α-glucosidase inhibitors, colesevelam, dopamine agonists, pramlintide) may be used where available in selected patients but have modest efficacy and/or limiting side effects. In patients intolerant of, or with contraindications for, metformin, select initial drug from other classes depicted, and proceed accordingly. Consider starting with 2-drug combinations in patients with very high HbA1c (e.g. ≥9%). T2DM Antihyperglycemic Therapy: General Recommendations Diabetes Care, Diabetologia. 19 April 2012

T2DM Antihyperglycemic Therapy: General Recommendations Further progression to 3-drug combinations are reasonable if 2-drug combinations do not achieve target. If metformin contraindicated or not tolerated, while published trials are generally lacking, it is reasonable to consider 3-drug combinations other than metformin. Insulin is likely to be more effective than most other agents as a third-line therapy, especially when HbA1c is very high (e.g. ≥9.0%). The therapeutic regimen should include some basal insulin before moving to more complex insulin strategies (see Fig. 3) T2DM Antihyperglycemic Therapy: General Recommendations Diabetes Care, Diabetologia. 19 April 2012

Ultimately, more intensive insulin regimens may be required (see Figure 3.) Dashed arrow line on the left-hand side of the figure denotes the option of a more rapid progression from a 2-drug combination directly to multiple daily insulin doses, in those patients with severe hyperglycaemia (e.g. HbA1c ≥10.0-12.0%). Consider beginning with insulin if patient presents with severe hyperglycemia (≥300-350 mg/dl [≥16.7-19.4 mmol/l]; HbA1c ≥10.0-12.0%) with or without catabolic features (weight loss, ketosis, etc). Diabetes Care, Diabetologia. 19 April 2012

Handling of pills Study in 119 home-living non-demented persons (81 years, 66% female) Nikolaus T et al (1996). Eur J Clin Pharmacol 49:255 packaging percentage of persons, who could not open package „Children safe bottle“ 44,5% Weekly dispenser 16,8 % Blister pack 10,1%

Number of interactions = i i = (n2 – n) / 2 n = number of drugs i = number of pairs of interaction e.g. 7 drugs gives 21 pairs of interaction to be respecteds Ca 20 % aller Krankenhauseinweisungen im Alter stehen im Zusammenhang mit Medikamentennebenwirkungen*1 Typische Manifestationen bzw. Symptome der unerwünschten Arzneimittelwirkungen im Alter sind*1: Psychische Störungen (z.B: Verwirrtheit, Depression, Denk- und Merkschwierigkeiten ...) Störungen des Mineral und Wasserhaushaltes (Hyponatriämie, Hypokalieämie, Exikose...) Motorische Störungen (Stürze, Ataxie, EPMS...) Herzkreislaufstörungen (Schwindel, Orthostase, Arythmien...) Urogastrointestinale Bschwerden (Obstipation, Übelkeit, Miktionsstörungen...) 1.) T. Herdegen in „Gerontoneurologie“, G. Deusch Hrg., Thieme-Verlag, Stuttgart 2006

Splitting tabletts

T2DM Antihyperglycemic Therapy: General Recommendations Moving from the top to the bottom of the figure, potential sequences of anti-hyperglycaemic therapy. In most patients, begin with lifestyle changes; metformin monotherapy is added at, or soon after, diagnosis (unless there are explicit contraindications). T2DM Antihyperglycemic Therapy: General Recommendations Diabetes Care, Diabetologia. 19 April 2012

Benefits far over glycemia (chronic heart failure, cancer, lipids) Class Mechanism Advantages Disadvantages Cost Biguanides Activates AMP-kinase  Hepatic glucose production Extensive experience No hypoglycemia Weight neutral ?  CVD Gastrointestinal Lactic acidosis B-12 deficiency Contraindications Low Metformin can be considered as first-line glucose-lowering therapy in older people with type 2 diabetes, and as an adjunct to insulin therapy in those recommended for combination therapy Personal Opinion: Metformin is safe if severe chronic kidney disease is ruled out and renal function is monitored by physician Benefits far over glycemia (chronic heart failure, cancer, lipids) Diabetes Care, Diabetologia. 19 April 2012 JAMDA Volume 13, Issue 6, Pages 497-502 July 2012

N=142.417 patients with T2DM Zeyfang, A. 1, Molz E. 2, Schütt M.3, Fach E. M.4, Siegel E.5, Holl R.W.2 Presentation at the annual meeting of the German Diabetes Association 19. Mai 2012

Therapy with Metformin at age>80y In Germany: 14 lactic acidosis per year N=3406 Pat. >80y with Metformin M 33% F 66%

Meglitinides (Glinids) are not mentioned Class Mechanism Advantages Disadvantages Cost SUs / Meglitinides Closes KATP channels  Insulin secretion Extensive experience  Microvasc. risk Hypoglycemia Weight gain Low durability ? Ischemic preconditioning Low Sulfonylurea In those patients at higher risk of hypoglycaemia, sulphonylurea therapy should be avoided Meglitinides (Glinids) are not mentioned First generation Carbutamide Acetohexamide Chlorpropamide Tolbutamide Tolazamide Second generation Glipizide Gliclazide Glibenclamide (glyburide) Glibornuride Gliquidone Glisoxepide Glyclopyramide Glimepiride Personal Opinion: Sulfonylureas should not be first choice drugs in older persons. Diabetes Care, Diabetologia. 19 April 2012 JAMDA Volume 13, Issue 6, Pages 497-502 July 2012 Roumie CL et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Annals of Internal Medicine 2012; 157: 601-10

Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study n= 364 865 patients Cumulative incidence (95% CIs) of cardiovascular disease or death. Roumie CL et al. Ann Intern Med. 2012;157(9):601-610.

Typical QT measurement with a screen cursor placement from a subject during euglycemia (left panel), showing a clearly defined T wave, and hypoglycemia (right panel), showing prolonged repolarization and a prominent U wave. Reproduced from Marques et al. (20) with permission from John Wiley & Sons. Typical QT measurement with a screen cursor placement from a subject during euglycemia (left panel), showing a clearly defined T wave, and hypoglycemia (right panel), showing prolonged repolarization and a prominent U wave. Copyright © 2011 American Diabetes Association, Inc. Frier B M et al. Dia Care 2011;34:S132-S137

Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus. Observational study from Kaiser Permanente Data 16.667 Typ 2 Diabetes mean 65 years HbA1c: 8,1% no Dementia 1.1.2003 1980 2007 Retrospective Prospective 1980-85 2005-07 Patients with Hypoglycemia: 1.465 (8,8%) Patients with Dementia: 1.822 (11 %) Whitmer RA et al. JAMA. 2009;301(15):1565-1572.

Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus. Kaiser Permanente Data 16.667 Typ 2 Diabetes Age: 65 years Average HbA1c: 8,1% No Dementia Adjusted for : Age, BMI, race, sex, Diabetes duration, 7-year HbA1c, Comorbidity, Mode of therapy, Duration on insulin Whitmer RA et al. JAMA. 2009;301(15):1565-1572.

Acarbose is not mentioned Class Mechanism Advantages Disadvantages Cost TZDs PPAR-g activator  insulin sensitivity No hypoglycemia Durability  TGs,  HDL-C ?  CVD (pio) Weight gain Edema / heart failure Bone fractures ?  MI (rosi) ? Bladder ca (pio) High a-GIs Inhibits a-glucosidase Slows carbohydrate absorption Nonsystemic  Post-prandial glucose ?  CVD events Gastrointestinal Dosing frequency Modest  A1c Mod. Thiazolidindiones (Glitazones) In selected patients not at high risk of heart failure or of bone loss or a previous diagnosis of osteoporosis, who have no history of bladder cancer, treatment with pioglitazone can be considered as second-line therapy after metformin. Acarbose is not mentioned Personal opinion: in old age not second, but third or fourth-line Diabetes Care, Diabetologia. 19 April 2012 JAMDA Volume 13, Issue 6, Pages 497-502 July 2012

Class Mechanism Advantages Disadvantages Cost Biguanides Activates AMP-kinase  Hepatic glucose production Extensive experience No hypoglycemia Weight neutral ?  CVD Gastrointestinal Lactic acidosis B-12 deficiency Contraindications Low SUs / Meglitinides Closes KATP channels  Insulin secretion  Microvasc. risk Hypoglycemia Weight gain Low durability ? Ischemic preconditioning TZDs PPAR-g activator  insulin sensitivity Durability  TGs,  HDL-C ?  CVD (pio) Edema / heart failure Bone fractures ?  MI (rosi) ? Bladder ca (pio) High a-GIs Inhibits a-glucosidase Slows carbohydrate absorption Nonsystemic  Post-prandial glucose ?  CVD events Dosing frequency Modest  A1c Mod. Diabetes Care, Diabetologia. 19 April 2012

Personal Opinion: very useful in treatment in old age Class Mechanism Advantages Disadvantages Cost DPP-4 inhibitors Inhibits DPP-4 Increases GLP-1, GIP No hypoglycemia Well tolerated Modest  A1c ? Pancreatitis Urticaria High GLP-1 receptor agonists Activates GLP-1 R  Insulin,  glucagon  gastric emptying  satiety Weight loss ? Beta cell mass ? CV protection GI Medullary ca Injectable Inhibitors of Dipeptidyl-Peptidase-4 (Gliptines) In selected older patients not in target or where there is poor tolerance to other glucose-lowering agents, the use of a DPP4-inhibitor can be considered as 2nd line therapy. GLP-1 Analogs (Mimetics) In subjects who are obese (BMI >35), where there is poor tolerance or lack of response to other agents, a GLP-1 agonist can be considered as both 2nd line and 3rd line therapy. Personal Opinion: very useful in treatment in old age Diabetes Care, Diabetologia. 19 April 2012 JAMDA Volume 13, Issue 6, Pages 497-502 July 2012

SGLT2-Inhibitors Chao EC, et al. Nat Rev Drug Discovery. 2010;9:551-559.

SGLT2-Inhibitor Dapagliflozin Was ist gesichert? Bailey et al., Lancet 2010; 375: 2223-2233

Personal Opinion: watchful waiting before used in old age Class Mechanism Advantages Disadvantages Cost SGLT-2-I Inhibition of glucose reabsorption No hypoglycemia Weight loss Additive action urinary tract infections thrush (candidiasis) hypotensive reactions High Glitazars Bardoxolon Salsalat Personal Opinion: watchful waiting before used in old age Urinary-genital infection Dehydration Diabetes Care, Diabetologia. 19 April 2012

http://en.wikipedia.org/wiki/ATC_code_A10

Ultimately, more intensive insulin regimens may be required (see Figure 3.) Dashed arrow line on the left-hand side of the figure denotes the option of a more rapid progression from a 2-drug combination directly to multiple daily insulin doses, in those patients with severe hyperglycaemia (e.g. HbA1c ≥10.0-12.0%). Consider beginning with insulin if patient presents with severe hyperglycemia (≥300-350 mg/dl [≥16.7-19.4 mmol/l]; HbA1c ≥10.0-12.0%) with or without catabolic features (weight loss, ketosis, etc). Diabetes Care, Diabetologia. 19 April 2012

Class Mechanism Advantages Disadvantages Cost Insulin Activates insulin receptor  peripheral glucose uptake Universally effective Unlimited efficacy  Microvascular risk Hypoglycemia Weight gain ? Mitogenicity Injectable Training requirements “Stigma” Variable Personal Opinion: Short acting insulin analogs Administration through caregivers more easily, in some studies less hypoglycemia Insulin Glargin Basal oriented therapy makes therapy more easy for patient and carers Insulin Degludec Long half-life, time of injection from day-to-day can be changed; shows less hypoglycemia Diabetes Care, Diabetologia. 19 April 2012 Diabetes Care, Diabetologia. 19 April 2012

IGF-1, GH and Insulin Schwarz=IGF-1 Weiss = Insulin Figure 4 This diagram illustrates our current understanding about the synergistic action between insulin, IGF-I and GH in regulating protein (P) synthesis. Without insulin, GH loses much (if not all) of its anabolic action. GH and IGF-I stimulate protein synthesis directly, while insulin is anabolic through inhibiting protein breakdown. The anabolic action of both GH and IGF-I appears to be mediated through induction of amino acid (Aa) transporters in the cell membrane. This is reflected in vivo by an increase in amino acid MCR. It is not yet clear how much of IGF-I’s action is through locally generated IGF-I (‘autocrine’ and ‘paracrine’) or through circulating IGF-I that is largely derived from the liver. Sonksen PH. Insulin, growth hormone and sport. Journal of Endocrinology (2001) 170, 13–25 32

Domains of Enquiry JAMDA Volume 13, Issue 6, Pages 497-502 July 2012 Hypoglycaemia Insulin therapy Care home diabetes Influence of comorbidity Glucose targets Family/carer perspectives Diabetes education Patient safety JAMDA Volume 13, Issue 6, Pages 497-502 July 2012

Estimated Rates of Emergency Hospitalizations for Adverse Drug Events in Older U.S. Adults, 2007–2009. Figure 1. Estimated Rates of Emergency Hospitalizations for Adverse Drug Events in Older U.S. Adults, 2007–2009. Estimates were based on hospitalization data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project for 2007 through 2009, and data for outpatient visits during which medications were ordered or continued are from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for 2007 and 2008. High-risk medications are those designated as such in the elderly by the 2011 Healthcare Effectiveness Data and Information Set (HEDIS).12 Potentially inappropriate medications are those identified by the updated 2002 Beers criteria for potentially inappropriate medication use in older adults. 13 All high-risk or potentially inappropriate medications were included in the analysis, regardless of the dose, frequency of use, formulation (e.g., short-acting), or duration of use. I bars denote 95% confidence intervals. For oral antiplatelet agents, the coefficient of variation was greater than 30%. Budnitz DS et al. N Engl J Med 2011;365:2002-2012.

Reduced awareness of hypoglycemia in older persons with T2DM Hypoglycemia 50 mg/dl for 30 min T2DM MW 51 years □ T2DM MW 70 years ■ Bremer JP et al. Diabetes Care july 2009 36 36

Sequential Insulin Strategies in T2DM Basal insulin alone is usually the optimal initial regimen, beginning at 0.1-0.2 U/kg body weight, depending on the degree of hyperglycemia. It is usually prescribed in conjunction with 1-2 non-insulin agents. In patients willing to take >1 injection and who have higher A1c levels (≥9.0%), BID pre-mixed insulin or a more advanced basal plus mealtime insulin regimen could also be considered (curved dashed arrow lines). When basal insulin has been titrated to an acceptable FPG but A1c remains above target, consider proceeding to basal + meal-time insulin, consisting of 1-3 injections of rapid-acting analogues. A less studied alternative—progression from basal insulin to a twice daily pre-mixed insulin—could be also considered (straight dashed arrow line); if this is unsuccessful, move to basal + mealtime insulin. The figure describes the number of injections required at each stage, together with the relative complexity and flexibility. Once a strategy is initiated, titration of the insulin dose is important, with dose adjustments made based on the prevailing BG levels as reported by the patient. Non-insulin agents may be continued, although insulin secretagogues (sulfonylureas, meglitinides) are typically stopped once more complex regimens beyond basal insulin are utilized. Comprehensive education regarding self-monitoring of BG, diet, exercise, and the avoidance of, and response to, hypoglycemia are critical in any patient on insulin therapy. Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012

Injecting insulin alone? Timed Test of money counting! Sufficient eye-sight Good fine motor skills Handling with numbers DIAMAN-Study Prediction of insulin self-management in older persons Nikolaus T, Bach M, Specht-Leible N, Oster P, Schlierf G. The Timed Test of Money Counting: a short physical performance test for manual dexterity and cognitive capacity. Age Ageing 1995;24:257-258

DIAMAN-Study Cut-Off at 45 s: PPV 75% n=100 patients >65 years with diabetes and geriatric syndromes Test and follow-up after 3 months Cut-Off at 45 s: PPV 75%

Primary goal in every age: Individuelle Lebensqualität – Rauchen, Trinken, Essen,schnelle Autos, Reisen Primary goal in every age: Quality of Life !